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Contents

AdvancedCardiacLifeSupport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
CriticalCarePatientManagement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
CriticalCareHistoryandPhysicalExamination . . . . . . . . . . . . . . . . . . . 15
Critical Care Physical Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Admission Check List . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Critical Care Progress Note . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
ProcedureNote . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Discharge Note . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
FluidsandElectrolytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
BloodComponentTherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Total Parenteral Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Enteral Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
RadiographicEvaluationofInterventions . . . . . . . . . . . . . . . . . . . . . . . . 20
Arterial Line Placement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
CentralVenousCatheterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
NormalPulmonaryArteryCatheterValues . . . . . . . . . . . . . . . . . . . . . . . 24
CardiovascularDisorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
AcuteCoronarySyndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
MyocardialInfarctionandUnstableAngina . . . . . . . . . . . . . . . . . . . . . . . 25
Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
AtrialFibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
HypertensiveEmergency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Ventricular Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
TorsadesdePointes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Acute Pericarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Pacemakers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
PulmonaryDisorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
OrotrachealIntubation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
NasotrachealIntubation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
VentilatorManagement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Inverse Ratio Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
VentilatorWeaning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
PulmonaryEmbolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
ChronicObstructivePulmonaryDisease . . . . . . . . . . . . . . . . . . . . . . . . 62
Pleural Effusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Pneumothorax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
TensionPneumothorax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
CardiacTamponade . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Pericardiocentesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
HematologicDisorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Transfusion Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
DisseminatedIntravascularCoagulation . . . . . . . . . . . . . . . . . . . . . . . . . 72
Thrombolytic-associatedBleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
InfectiousDiseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Bacterial Meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
PneumocystisCariniiPneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
AntiretroviralTherapyandOpportunisticInfectionsinAIDS . . . . . . . . . . 85
Sepsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Peritonitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Gastroenterology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
UpperGastrointestinalBleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
VaricealBleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
LowerGastrointestinalBleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Acute Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
HepaticEncephalopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Toxicology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
PoisoningandDrugOverdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Toxicologic Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
AcetaminophenOverdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Cocaine Overdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
CyclicAntidepressantOverdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Digoxin Overdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
EthyleneGlycolIngestion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
Gamma-hydroxybutyrateIngestion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Iron Overdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
IsopropylAlcoholIngestion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Lithium Overdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
MethanolIngestion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Salicylate Overdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
TheophyllineToxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
Warfarin (Coumadin) Overdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
NeurologicDisorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Ischemic Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Elevated Intracranial Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Status Epilepticus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
EndocrinologicandNephrologicDisorders . . . . . . . . . . . . . . . . . . . . . 125
DiabeticKetoacidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
AcuteRenalFailure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Hyperkalemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
Hypokalemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Hypomagnesemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
Hypermagnesemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
DisordersofWaterandSodiumBalance . . . . . . . . . . . . . . . . . . . . . . . 136
Hypophosphatemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
Hyperphosphatemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
CommonlyUsedFormulas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
CommonlyUsedDrugLevels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
AdvancedCardiacLifeSupport
EMERGENCYCARDIACCARE
Ifwitnessedarrest,give
precordialthumpand
checkpulse. Ifabsent,
continueCPR
Assess Responsiveness
Unresponsive
CallforcodeteamandDefibrillator
Assessbreathing(opentheairway, look,
listenandfeelforbreathing)
IfNotBreathing,
givetwoslowbreaths.
AssessCirculation
PULSE NOPULSE
InitiateCPR
Giveoxygenbybagmask
SecureIVaccess
Determineprobableetiologyofarrest
basedonhistory,physicalexam,cardiac
monitor,vitalsigns,and12leadECG.
Ventricular
fibrillation/tachycardia
(VT/VF)presenton
monitor?
Hypotension/shock,
acutepulmonary
edema.
Gotofig8
NO YES
Intubate
Confirmtubeplacement
Determinerhythmand
cause.
VT/VF
GotoFig2
Arrhythmia
Bradycardia
GotoFig5
Tachycardia
GotoFig6
ElectricalActivity?
YES
NO
Pulselesselectricalactivity
GotoFig3
Asystole
GotoFig4
Fig1- Algorithm forAdultEmergencyCardiacCare
VENTRICULARFI BRILLATIONANDPULSELESS
VENTRICULARTACHYCARDI A
ContinueCPR
Persistent or
recurrentVF/VT
Epinephrine1mg
IVpush,repeat
q3-5minor2mgin
10mlNSviaETtube
q3-5minor
Vasopressin40UIVPx
1 doseonly
Defibrillate360J
Amiodarone(Cordarone) 300mgIVPor
Lidocaine1.5mg/kgIVP,andrepeatq3-5min,uptototalmax of3 mg/kgor
Magnesiumsulfate(ifTorsadedepointes orhypomagnesemic)2gms IVPor
Procainamide (if aboveareineffective)30mg/minIVinfusion tomax17mg/kg
ContinueCPR
Secure IVaccess
Intubateif no response
Defibrillateimmediately,upto3times at 200J, 200-300J, 360J.
Donot delaydefibrillation
Returnof
spontaneous
circulation
PulselessElectrical
Activity
GotoFig3
Monitorvitalsigns
Supportairway
Supportbreathing
Providemedicationsappropriateforblood
pressure, heartrate,andrhythm
AssessAirway,Breathing, Circulation,Differential Diagnosis
AdministerCPRuntildefibrillatorisready(precordialthumpifwitnessedarrest)
VentricularFibrillationor Tachycardiapresentondefibrillator
Asystole
GotoFig4
CheckpulseandRhythm
ContinueCPR
Defibrillate 360J, 30-60 secondsaf tereachdose of medication
Repeat amiodarone(Cordarone)150mgIVPprn(ifreurrent VF/VT),uptomax
cumulativedoseof2200mgin24 hours
Continue CPR. Administersodiumbicarbonate1mEq/kgIVPiflongarrestperiod
Repeat patternofdrug-shock,drug-shock
Note:Epinephrine,lidocaine, atropinemay begivenviaendot rachealt ubeat
2-2.5t imes theIVdose. Dilute in10ccof saline.
Aftereachintravenousdose, give 20-30mLbolus of IVf luidandelevat e
extremity.
Fig2 - VentricularFibrillationandPulseless VentricularTachycardia
PULSELESSELECTRICALACTIVITY
PulselessElectrical Activity Includes:
Electromechanicaldissociation(EMD)
Pseudo-EMD
Idioventricular rhythms
Ventricularescaperhythms
Bradyasystolic rhythms
Postdefibrillationidioventricular rhythms
Epinephrine1.0mgIVbolusq3-5min,orhighdose
epinephrine0.1mg/kgIVpushq3-5min; maygivevia
ETtube.
ContinueCPR
Ifbradycardia(<60beats/min),giveatroprine1mgIV,q3-5
min,uptototalof 0.04mg/kg
Considerbicarbonate, 1mEq/kgIV(1-2amp, 44mEq/amp),
ifhyperkalemiaorotherindications.
Determinedifferentialdiagnosisandtreatunderlyingcause:
Hypoxia(ventilate)
Hypovolemia(infusevolume)
Pericardial tamponade(performpericardiocentesis)
Tensionpneumothorax(performneedledecompression)
Pulmonaryembolism(thrombectomy,thrombolytics)
Drugoverdosewithtricyclics,digoxin,beta,or calciumblockers
Hyperkalemiaorhypokalemia
Acidosis(givebicarbonate)
Myocardialinfarction(thrombolytics)
Hypothemia(activerewarming)
InitiateCPR,secureIVaccess,intubate,assesspulse.
Fig3- PulselessElectrical Activity
ASYSTOLE
ContinueCPR.Confirmasystoleby
repositioningpaddlesorbychecking2leads.
IntubateandsecureIVaccess.
Considerunderlyingcause, suchashypoxia,
hyperkalemia,hypokalemia,acidosis,drug
overdose, hypothermia.myocardialinfarction.
Consider transcutaneouspacing(TCP)
Atropine1mgIV,repeatq3-5minuptoatotalof
0.04mg/kg;maygiveviaETtube.
Epinephrine1.0mgIVpush,repeatevery3-5min;
maygivebyETtube;highdoseepinephrine0.1
mg/kgIVpushq5min(1:1000sln).
Consider bicarbonate1mEq/kg(1-2amp)if
hyperkalemia, acidosis, tricyclicoverdose.
Consider terminationofefforts.
Fig4- Asystole
BRADYCARDIA
No
Yes
Yes No
AssessAirway,Breathing,Circulation, Assessvitalsigns
Differential Diagnosis Reviewhistory
Secureairwayandgiveoxygen Performbriefphysical exam
SecureIVaccess Order 12-leadECG
Attachmonitor, pulseoximeterand
automaticsphygmomanometer
Tooslow(<60beats/min)
Bradycardia(<60beats/min)
SeriousSignsorSymptoms?
If typeII secondor 3rddegreeheart block,
widecomplexescapebeats,MI/ischemia,
denervatedheart(transplant),newbundle
branchblock:InitiatePacing(transcutanous
or venous)
If typeIseconddegreeheart block, give
atropine0.5-1.0mgIV, repeat q5min,then
initiatepacingifbradycardia.
Dopamine5-20:g/kgperminIVinfusion
Epinephrine2-10mcg/minIVinfusion
Isoproterenol2-10mcg/minIVinfusion
Observe
Consider transcutaneouspacingor transvenous
pacing.
TypeIIseconddegreeAVheart
blockor thirddegreeAV heart
block?
Fig 5-Bradycardia(withpatient not incardiacarrest).
Noorborderline
Atrial fibrillation
Atrialflutter
TACHYCARDIA
Paroxysmal
supraventricular
narrowcomplex
tachycardia
(PSVT)
Wide-complex
tachycardiaof
uncertaintype
Ventricular
tachycardia (VT)
Torsadedepointes
(polymorphicVT)
DetermineEtiology:Hypoxia,ischemia,
MI,pulmonaryembolus,
hyperthyroidism,electrolyteabnomality,
theophylline,inotropes.
IfuncertainifVtach,
giveAdenosine6
mgrapidIVpush
over 1-3sec
Amiodarone150-
300mgIVover10-
20min
Adenosine
12mg,rapidIV
pushover1-3sec
(mayrepeatonce
in1-2min)
1-2 min
Adenosine
6mg,rapidIV
pushover1-3sec
1-2min
Cardioversionofatrialfibrillationtosinusrhythm:
Ifless than 2 daysandratecontrolled:
Procainamideoramiodarone,followedby
cardioversion
Ifmorethan2days: Coumadinfor3weeks;
controlrate,startantiarrythmicagent,then
electrical cardioversion.
ControlRate:Diltiazem,verapamil,digoxin
esmolol,metoprolol
Yes
AssessAirway,Breathing,Circulation,DifferentialDiagnosis
AssessVitals, SecureAirway
Reviewhistoryandexaminepatient.
Give100%oxygen,secureIVaccess.
AttachECGmonitor,pulseoximeter,bloodpressuremonitor.
Order12-leadECG,portablechestx-ray.
Correctunderlying
cause:Hypokal-
emia, drugover-
dose (tricyclic,
phenothiazine,
antiarrhythmic
classIa,Ic,III)
UNSTABLE, withserioussignsorsymptoms?
Unstableincludes,hypotension,heartfailure,chestpain,myocardial
infarction,decreasedmentalstatus,dyspnea
IMMEDIATECARDIOVERSION
Atrialflutter50J,paroxysmalsupraventriculartachycardia
50J,atrialfibrillation 100J,monomorphicventricular
tachycardia100J,polymorphic Vtach200J.
Premedicatewithmidazolam(Versed) 2-5mgIVPwhen
possible.
Vagalmaneuvers:
Carotidsinus
massageifno
bruits
Fig6Tachycardia
Ade nosi ne 12 mg, rapi d IV
push over 1-3 seconds(may
repea t once i n 1 -2 mi n); max
total 30 mg
L id ocai ne
1 -1.5 mg/kg IV push.
Repeat 0.5-0.75
mg/kg IVP q5- 10mi n
to maxtotal 3 mg/kg
Magne si um 2- 4 gm IV
o ver5 -10 mi n
Overdri ve paci ng
(cutaneous orvenous)
Isoproterenol 2-20 mcg/mi n
OR
Phenytoi n 15 mg/kg IV at 50
mg /mi n OR
L id ocai ne 1 .0 -1.5 mg/kg IVP
Cardioversi on 200 J
Procai n ami d e 30
mg/mi n IV to max
total 17 mg/kg
L id ocai ne 1 .0 -1.5 mg/kg IVP
Compl ex wi dth?
Narrow Wi de
If Wolf-Parki nson- Whi te
syndrome, gi ve ami odarone
(Cordarone) 150-300 mg IV
o ver 1 0- 20 mi n
Procai nami de
20- 30 mg/mi n, maxtotal17mg/kg;
fol l owed by2-4 mg/mi n infusi on
If WPW,a voi d a deno si ne,b eta-
blockers, calcium- bl ockers, and
d ig oxi n
Synchroni zed cardioversi on 100J
Normal or el evated pressure L ow- unstabl e
Verapami l
2 .5- 5 mg IV
1 5-30 m i n
Verapami l
5-10 mgI V
Consi der
Di goxi n
Beta blockers
Di lti azem
Overdri ve
p aci ng F i g 6 - T a chyc ard ia
Blood Pressure?
STABLETACHYCARDIA
Ifventricularrateis>150beats/min,prepareforimmediatecardioversion.
TreatmentofStablePatientsisbasedonArrhythmiaType:
VentricularTachycardia:
Procainamide(Pronestyl)30mg/minIV,uptoatotalmaxof17mg/kg,
or
Amiodarone(Cordarone)150-300mgIVover10-20min,or
Lidocaine0.75mg/kg. Procainamideshouldbeavoidedifejection
fractionis<40%.
ParoxysmalSupraventricularTachycardia: Carotidsinuspressure(if
bruitsabsent),thenadenosine6mgrapidIVP,followedby12mgrapid
IVPx2dosestomaxtotal30mg. Ifnoresponse,verapamil2.5-5.0mg
IVP;mayrepeatdosewith5-10mgIVPifadequatebloodpressure;or
Esmolol500mcg/kgIVover1min,then50mcg/kg/minIVinfusion,and
titrateupto200mcg/kg/minIVinfusion.
AtrialFibrillation/Flutter:
Ejectionfraction$40%:Diltiazem(Cardiazem)0.25mg/kgIVover2
min;mayrepeat0.35mg/kgIVover2minprnx1tocontrolrate. Then
giveprocainamide(Pronestyl)30mg/minIVinfusion,uptoatotalmax
of17mg/kg
Ejectionfraction<40%:Digoxin0.5mgIVP,then0.25mgIVPq4hx2
tocontrolrate. Thengiveamiodarone(Cordarone)150-300mgIVover
10-20min.
Stabletachycardiawithserioussignsand
symptomsrelatedtothetachycardia. Patient
notincardiacarrest.
Checkoxygensaturation,suctiondevice,
intubationequipment. SecureIVaccess
Synchronizedcardioversion
Atrialflutter 50J
PSVT 50J
Atrial 100J
MonomorphicV-tach 100J
PolymorphicVtach 200J
PremedicatewheneverpossiblewithMidazolam(Versed)
2-5mgIVPorsodiumpentothal2mg/kgrapidIVP
Fig7- StableTachycardia (notincardiacarrest)
HYPOTENSION, SHOCK, ANDACUTEPULMONARYEDEMA
S y s tol ic BP
70- 100 mm Hg
Dopam i n e 2 . 5- 20
: g /k g p e r mi n I V
(ad d n o rep i nephrine
i f d o pami n e is >20
: g /k g p e r mi n )
Norepi n e p hri ne 0 . 5 -
3 0 : g / mi n IV o r
Do p a mi ne 5 - 20 : g / kg
p e r mi n
B radycardi a
G o to Fi g 5
SystolicBP>100mm Hg
anddiastolicBPnormal
Syst o l ic B P
<7 0 mm Hg
DiastolicBP>110mmHg
Dobutam i ne 2 .0 - 20
: g / kg per mi n I V
Furosem i de I V 0.5- 1 . 0 mg/ kg
Morph i n e IV 1 - 3 mg
Ni trogl yceri n SL 0 .4 m g tab
q 3 - 5m i n x 3
O xygen
T a chycardi a
Go t o Fi g 6
Det e r mi n e b l ood pre s sure
Determi ne u n d e rl yin g ca u s e
H y pov olem ia
Pum p F a ilu r e
B ra dy c a r dia o r Tac h y c a r dia
Adm in i ster Flu i ds, Bl ood
Co n s i d e r vaso p r essors
Appl y hemostasi s; t r e a t
u n d e r l yi ng prob l e m
If i sche mi a a n d hyp e rtensi o n :
Ni tro g l yce r i n1 0 -2 0 : g /m i n
I V, a n d t it r at e to ef f e c t and/or
Nitro p russi d e 0 . 1 -5.0
: g /kg/mi n I V
Signsandsymptomsofcongestiveheartfailure,acutepulmonaryedema.
AssessABCD's,secureairway,administeroxygen;secureIVaccess. MonitorECG,pulseoximeter,
bloodpressure,order12-leadECG,portablechestX-ray
Checkvitalsigns, reviewhistory,andexaminepatient.Determinedifferential diagnosis.
Fig8- Hypotension, Shock,andAcutePulmonaryEdema
14CriticalCareHistoryandPhysicalExamination
CriticalCareHistoryandPhysicalExamination15
Critical Care Patient Management
T.ScottGallacher,MD,MS
CriticalCareHistoryandPhysicalExamination
Chiefcomplaint:ReasonforadmissiontotheICU.
Historyofpresentillness:Thissectionshouldincludedpertinentchronological
events leading up to the hospitalization. It should include events during
hospitalizationandeventualadmissiontotheICU.
Prior cardiac history: Angina (stable, unstable, changes in frequency),
exacerbatingfactors(exertional,restangina).Historyofmyocardialinfarction,
heart failure, coronary artery bypass graft surgery, angioplasty. Previous
exercisetreadmilltesting,ECHO,ejectionfraction.RequestoldECG,ECHO,
impedancecardiography,stresstestresults,andangiographicstudies.
Chestpaincharacteristics:
A. Pain:Qualityofpain,pressure,squeezing,tightness
B. Onsetofpain:Exertional,awakeningfromsleep,relationshiptoactivities
ofdailyliving(ADLs),suchaseating,walking,bathing,andgrooming.
C. Severityandquality:Pressure,tightness,sharp,pleuritic
D. Radiation:Arm,jaw,shoulder
E. Associatedsymptoms:Diaphoresis,dyspnea,backpain,GI symptoms.
F. Duration:Minutes,hours,days.
G. Relievingfactors:Nitroclycerine,rest.
Cardiac risk factors: Age, male, diabetes, hypercholesteremia, low HDL,
hypertension, smoking, previous coronary artery disease, family history of
arteriosclerosis(eg,myocardialinfarctioninmaleslessthan50years old,
stroke).
Congestiveheartfailuresymptoms:Orthopnea(numberofpillows),paroxys-
malnocturnaldyspnea,dyspneaonexertional,edema.
Peripheral vascular disease symptoms: Claudication, transient ischemic
attack,cerebralvascularaccident.
COPDexacerbationsymptoms:Shortnessofbreath,fever,chills,wheezing,
sputum production, hemoptysis (quantify), corticosteroid use, previous
intubation.
Pastmedicalhistory:Pepticulcerdisease,renaldisease,diabetes,COPD.
Functionalstatuspriortohospitalization.
Medications:Doseandfrequency. Useofnitroglycerine,beta-agonist,steroids.
Allergies: Penicillin, contrast dye, aspirin; describe the specific reaction (eg,
anaphylaxis,wheezing,rash,hypotension).
Socialhistory:Tobaccouse,alcoholconsumption,intravenousdruguse.
Reviewofsystems:Reviewsymptomsrelatedtoeachorgansystem.
CriticalCarePhysicalExamination
Vitalsigns:
Temperature, pulse, respiratory rate, BP (vital signs should be given in
ranges)
Input/Output:IVfluidvolume/urineoutput.
16AdmissionCheckList
Specialparameters:Oxygensaturation,pulmonaryarterywedgepressure
(PAWP),systemicvascularresistance(SVR),ventilatorsettings,impedance
cardiography.
General:Mentalstatus,Glasgowcomascore,degreeofdistress.
HEENT:PERRLA,EOMI,carotidpulse.
Lungs:Inspection,percussion,auscultationforwheezes,crackles.
Cardiac: Lateral displacement of point of maximal impulse; irregular rate,,
irregular rhythm (atrial fibrillation); S3 gallop (LV dilation), S4 (myocardial
infarction),holosystolicapexmurmur(mitralregurgitation).
Cardiacmurmurs:1/6=faint;2/6=clear;3/6-loud;4/6=palpable;5/6=heard
withstethoscopeoffthechest;6/6=heardwithoutstethoscope.
Abdomen:Bowelsoundsnormoactive,abdomensoftandnontender.
Extremities:Cyanosis,clubbing,edema,peripheralpulses2+.
Skin:Capillaryrefill,skinturgor.
Neuro
Deficitsinstrength,sensation.
Deeptendonreflexes:0=absent;1=diminished;2=normal;3=brisk;4=
hyperactiveclonus.
MotorStrength:0=nocontractility;1=contractilitybutnojointmotion;2 =
motion without gravity; 3 = motion against gravity; 4 = motion against
someresistance;5=motionagainstfullresistance(normal).
Labs: CBC, INR/PTT; chem 7, chem 12, Mg, pH/pCO
2
/pO
2
. CXR, ECG,
impedancecardiography,otherdiagnosticstudies.
Impression/Problem list: Discuss diagnosis and plan for each problem by
system.
NeurologicProblems:Listanddiscussneurologicproblems
PulmonaryProblems:Ventilatormanagement.
CardiacProblems:Arrhythmia,chestpain,angina.
GIProblems:H2blockers,nasogastrictubes,nutrition.
GenitourinaryandElectrolytesProblems:Fluidstatus:IVfluids,electrolyte
therapy.
HematologicProblems:Bloodorbloodproducts,DVTprophylaxis.
InfectiousDisease:Plansforantibiotictherapy;antibioticdaynumber,culture
results.
Endocrine/Nutrition:Serumglucosecontrol,parenteralorenteralnutrition,diet.
AdmissionCheckList
1. Callandrequestoldchart,ECG,andx-rays.
2. Statlabs:CBC,chem7,cardiacenzymes(myoglobin,troponin,CPK),INR,
PTT,C&S,ABG,UA,cardiacenzymes(myoglobin,troponin,CPK).
3. Labs:Toxicologyscreensanddruglevels.
4. Cultures: Blood culture x 2, urine and sputum culture (before initiating
antibiotics),sputumGramstain,urinalysis.
5. CXR,ECG,diagnosticstudies.
6. Discusscasewithresident,attending,andfamily.
CriticalCareProgressNote17
CriticalCareProgressNote
ICUDayNumber:
AntibioticDayNumber:
Subjective:Patientis awakeandalert.Noteanyeventsthatoccurredovernight.
Objective:Temperature,maximumtemperature,pulse,respiratoryrate,BP,24-
hr input and output, pulmonary artery pressure, pulmonary capillary wedge
pressure,cardiacoutput.
Lungs:Clearbilaterally
Cardiac:Regularrateandrhythm,nomurmur,norubs.
Abdomen:Bowelsoundsnormoactive,soft-nontender.
Neuro:Nolocaldeficitsinstrength,sensation.
Extremities:Nocyanosis,clubbing,edema,peripheralpulses2+.
Labs:CBC,ABG,chem7.
ECG: Chestx-ray:
ImpressionandPlan:Giveanoverallimpression,andthendiscussimpression
andplanbyorgansystem:
Cardiovascular:
Pulmonary:
Neurological:
Gastrointestinal:
Infectious:
Endocrine:
Nutrition:
ProcedureNote
Aprocedurenoteshouldbewritteninthechartwhenaprocedureisperformed.
Procedurenotesarebriefoperativenotes.
ProcedureNote
18DischargeNote
Dateandtime:
Procedure:
Indications:
PatientConsent:Documentthattheindications,risksandalternativesto
theprocedurewereexplainedtothepatient.Notethatthepatientwas
giventheopportunitytoaskquestionsandthatthepatientconsentedto
theprocedureinwriting.
Labtests:Relevantlabs,suchastheINRandCBC
Anesthesia:Localwith2%lidocaine
DescriptionofProcedure:Brieflydescribetheprocedure,including
sterileprep,anesthesiamethod,patientposition,devicesused,anatomic
locationofprocedure,andoutcome.
ComplicationsandEstimatedBloodLoss(EBL):
Disposition:Describehowthepatienttoleratedtheprocedure.
Specimens:Describeanyspecimensobtainedandlabstestswhichwere
ordered.
NameofPhysician:Nameofpersonperformingprocedureandsupervis-
ingstaff.
DischargeNote
Thedischargenoteshouldbewritteninthepatientschartpriortodischarge.
DischargeNote
Date/time:
Diagnoses:
Treatment:Brieflydescribetherapyprovidedduringhospitalization,
includingsurgicalproceduresandantibiotictherapy.
StudiesPerformed:Electrocardiograms,CTscans.
Dischargemedications:
Follow-upArrangements:
FluidsandElectrolytes
MaintenanceFluidsGuidelines:
70kgAdult:D51/4NSwith20mEqKCI/Literat125mL/hr.
SpecificReplacementFluidsforSpecificLosses:
Gastric(nasogastrictube,emesis):D5NSwith20mEq/LKCL.
Diarrhea:D5LRwith15mEq/literKCI.Provide1literofreplacementfor
each1kgor2.2lbofbodyweightlost.
Bile:D5LRwith25mEq/liter(amp)ofsodiumbicarbonate.
Pancreatic:D5LRwith50mEq/liter(1amp)sodiumbicarbonate.
BloodComponentTherapy19
BloodComponentTherapy
A. Packed red blood cells (PRBCs). Each unit provides 250-400 cc of
volume, and each unit should raise hemoglobin by 1 gm/dL and
hematocritby3%.PRBCsareusuallyrequestedintwounitincrements.
B. Typeandscreen.BloodistestedforA,B,Rhantigens,andantibodies
todonorerythrocytes.Ifbloodproductsarerequired,thebloodcanbe
rapidlypreparedbythebloodbank.Onegativebloodisusedwhentype
andscreeninformationisnotavailable,buttheneedfortransfusionis
emergent.
C. Type and cross match sets aside specific units of packed donor red
bloodcells.Ifbloodisneededonanurgentbasis,typeandcrossshould
berequested.
D. Platelets.Indicatedforbleedingifthereisthrombocytopeniaorplatelet
dysfunctioninthesettingofuncontrolledbleeding.Eachunitofplatelet
concentrateshouldraisetheplateletcountby5,000-10,000.Plateletsare
usuallytransfused6-10unitsatatime,whichshouldincreasetheplatelet
countby40-60,000.Thrombocytopeniaisdefinedasaplateletcountof
lessthan60,000.Forsurgery,thecountshouldbegreaterthan50,000.
E. FreshFrozenPlasma(FFP)isusedforactivebleedingsecondaryto
liver disease, warfarin overdose, dilutional coagulopathy secondary to
multiplebloodtransfusions,disseminatedintravascularcoagulopathy,and
vitamin K and coagulation factor deficiencies. Administration of FFP
requiresABOtyping,butnotcrossmatching.
1. Eachunitcontainscoagulationfactorsinnormalconcentration.
2. Twotofourunitsareusuallyrequiredfortherapeuticintervention.
F. Cryoprecipitate
1. IndicatedinpatientswithHemophiliaA,VonWillebrand'sdisease,and
any state of hypofibrinogenemia requiring replacement (DIC), or
reversalofthrombolytictherapy.
2. Cryoprecipitate contains factor VIII, fibrinogen, and Von Willebrand
factor.Thegoaloftherapyis tomaintainthefibrinogenlevelabove
100 mL/dL, which is usually achieved with 10 units given over 3-5
minutes.
TotalParenteralNutrition
Infuse40-50mL/hrofaminoaciddextrosesolutioninthefirst24hr;increase
dailyby40mL/hrincrementsuntilproviding1.3-2xbasalenergyrequirement
and1.2-1.7gmprotein/kg/d(seeformula,page142)
StandardSolutionperLiter
Aminoacidsolution(Aminosyn)7-10%
Dextrose40-70%
Sodium
Potassium
Chloride
Calcium
Phosphate
Magnesium
Acetate
500mL
500mL
35mEq
36mEq
35mEq
4.5mEq
9mMol
8.0mEq
82-104mEq
20EnteralNutrition
Multi-TraceElementFormula 1mL/d
Regularinsulin(ifindicated) 10-20U/L
Multivitamin12(2amp) 10mL/d
VitaminK(insolution,SQ,IM) 10mg/week
VitaminB12 1000mcg/week
FatEmulsion:
-Intralipid20%500mL/dIVPBinfusedinparallelwithstandardsolutionat1
mL/minx15min;ifnoadversereactions,increaseto20-50mL/hr.Serum
triglyceridelevelshouldbe checked6hafterendofinfusion(maintain
<250mg/dL).
CyclicTotalParenteralNutrition
-12-hournightschedule;tapercontinuousinfusioninmorningbyreducingrate
tohalforiginalratefor1hour.Furtherreduceratebyhalfforanadditional
hour,thendiscontinue.RestartTPNinevening.Taperatbeginningand
endofcycle.Finalrateshouldbe185mL/hrfor9-10hwith2hoursof
taperateachend,fortotalof2000mL.
PeripheralParenteralSupplementation
-Aminoacidsolution(ProCalamine)3%upto3L/dat125cc/hOR
-Combine500mLaminoacidsolution7%or10%(Aminosyn)and500mL
20% dextrose and electrolyte additive. Infuse at up to 100 cc/hr in
parallelwithintralipid10%or20%at1mL/minfor15min(testdose);
ifnoadversereactions,infuse500mL/dat20mL/hr.
SpecialMedications
-Famotidine(Pepcid)20mgIVq12hor40mg/dayinTPNOR
-Ranitidine(Zantac)50mgIVq6-8h.
-InsulinslidingscaleorcontinuousIVinfusion.
Labs
Baseline:Drawlabsbelow.Chestx-ray,plainfilmfortubeplacement
DailyLabs:Chem7,osmolality,CBC,cholesterol,triglyceride(6hafterend
ofinfusion),serumphosphate,magnesium, calcium,urinespecificgravity.
Weekly Labs: Protein, iron, TIBC, INR/PTT, 24h urine nitrogen and
creatinine. Pre-albumin, transferrin, albumin, total protein, AST, ALT,
GGT,alkalinephosphatase,LDH,amylase,totalbilirubin.
EnteralNutrition
GeneralMeasures:Dailyweights,nasoduodenalfeedingtube.Headofbedat
30degreeswhileenteralfeedingand2hoursaftercompletion.Recordbowel
movements.
Continuous Enteral Infusion: Initial enteral solution (Osmolite, Pulmocare,
Jevity)30mL/hr.Measureresidualvolumeq1hx12h,thentid;holdfeeding
for 1 h if residual is more than 100 mL of residual. Increase rate by 25-50
mL/hrat24hrintervalsastolerateduntilfinalrateof50-100mL/hr(1cal/mL)
astolerated.Threetablespoonsofproteinpowder(Promix)maybeaddedto
each500ccofsolution.Flushtubewith100ccwaterq8h.
Enteral Bolus Feeding: Give 50-100 mL of enteral solution (Osmolite,
Pulmocare,Jevity)q3hinitially.Increaseamountin50mLstepsto maxof
250-300mLq3-4h;30kcalofnonproteincalories/dand1.5gmprotein/kg/d.
Beforeeachfeeding measureresidualvolume,anddelayfeedingby1hif
>100mL.Flushtubewith100ccofwateraftereachbolus.
SpecialMedications:
RadiographicEvaluationofInterventions21
-Metoclopramide(Reglan)10-20mgPO,IM,IV,orinJtubeq6h.
-Famotidine(Pepcid)20mgJ-tubeq12hOR
-Ranitidine(Zantac)150mginJ-tubebid.
SymptomaticMedications:
-Loperamide(Imodium)24mgPOorinJ-tubeq6h,max16mg/dprnOR
-Diphenoxylate/atropine(Lomotil)5-10mL(2.5mg/5mL)POorinJ-tubeq4-
6h,max12tabs/dOR
-Kaopectate30ccPOorinJ-tubeq6h.
RadiographicEvaluationofInterventions
I. Centralintravenouslines
A. Centralvenouscathetersshouldbelocatedwellabovetherightatrium,
andnotinaneckvein.Ruleoutpneumothoraxbycheckingthatthelung
markingsextendcompletelytotheribcagesonbothsides.Examinefor
hydropericardium(waterbottlesign,mediastinalwidening).
B. Pulmonary artery catheter tips should be located centrally and
posteriorly,andnotmorethan3-5cmfrommidline.
II. Endotrachealtubes.Verifythatthetubeislocated3cmbelowthevocal
cordsand2-4cmabovethecarina;thetipoftubeshouldbeatthelevelof
aorticarch.
III. Tracheostomies. Verify by chest x-ray that the tube is located halfway
betweenthestomaandthecarina;thetubeshouldbeparalleltothelong
axisofthe trachea.Thetubeshouldbeapproximately2/3ofwidthofthe
trachea;thecuffshouldnotcausebulgingofthetracheawalls.Checkfor
subcutaneousairinthenecktissueandformediastinalwideningsecondary
toairleakage.
IV.Nasogastrictubesandfeedingtubes.Verify thatthetubeisinthestomach
andnotcoiledintheesophagusortrachea.Thetipofthetubeshouldnotbe
nearthegastroesophagealjunction.
V. Chesttubes.Achesttubeforpneumothoraxdrainageshouldbenearthe
level of the third intercostal space. If the tube is intended to drain a free-
flowingpleuraleffusion,itshouldbelocatedinferior-posteriorly,atorabout
theleveloftheeighthintercostalspace.Verifythatthesideportofthetube
iswithinthethorax.
VI.Mechanical ventilation. Obtain a chest x-ray to rule out pneumothorax,
subcutaneous emphysema, pneumomediastinum, or subpleural air cysts.
Lunginfiltratesoratelectasis maydiminishordisappear after initiation of
mechanical ventilationbecauseofincreasedaerationoftheaffectedlung
lobe.
ArterialLinePlacement
Procedure
1. Obtaina20-gauge1-2inchcatheteroverneedleassembly(Angiocath),
arterial line setup (transducer, tubing and pressure bag containing
heparinizedsaline),armboard,steriledressing,lidocaine,3ccsyringe,25-
gaugeneedle,and3-Osilksuture.
22CentralVenousCatheterization
2. Theradialarteryisthemostfrequentlyusedartery.UsetheAllentesttoverify
thepatencyoftheradialandulnararteries.Placetheextremityonanarm
boardwithagauzerollbehindthewristtomaintainhyperextension.
3. Preptheskinwithpovidone-iodineanddrape;infiltrate1%lidocaineusinga
25-gauge needle. Choose a site where the artery is most superficial and
distal.
4. Palpatethearterywiththelefthand,andadvancethecatheter-over-needle
assemblyintothearteryata30-degreeangletotheskin.Whenaflashof
bloodisseen,holdtheneedleinplace and advancethecatheterintothe
artery.Occludethearterywithmanualpressurewhilethepressuretubingis
connected.
5. Advancetheguidewireintotheartery,andpassthecatheterovertheguide
wire.Suturethecatheterinplacewith3-0silkandapplydressing.
CentralVenousCatheterization
I. Indicationsforcentralvenouscathetercannulation:Monitoringofcentral
venous pressures in shock or heart failure; management of fluid status;
insertion of a transvenous pacemaker; administration of total parenteral
nutrition;administrationofvesicants(chemotherapeuticagents).
II. Location: The internal jugular approach is relatively contraindicated in
patients with a carotid bruit, stenosis, or an aneurysm. The subclavian
approachhasanincreasedriskofpneumothoraxinpatientswithemphysema
orbullae.Theexternaljugularorinternaljugularapproachispreferablein
patients with coagulopathy or thrombocytopenia because of the ease of
externalcompression.Inpatientswithunilaterallungpathologyorachest
tubealreadyinplace,thecathetershouldbeplacedonthesideofpredomi-
nantpathologyoronthesidewiththechesttubeifpresent.
III. Techniqueforinsertionofexternaljugularveincatheter
1. The external jugular vein extends from the angle of the mandible to
behindthemiddleoftheclavicle,whereitjoinswiththesubclavianvein.
Placethepatientin Trendelenburg'sposition.CleanseskinwithBetadine-
iodine solution, and, using sterile technique, inject 1% lidocaine to
produceaskinweal.Applydigitalpressuretotheexternaljugularvein
abovetheclavicletodistendthevein.
2. Witha16-gaugethinwallneedle,advancetheneedleintothevein.Then
passaJ-guidewirethroughtheneedle;thewireshouldadvancewithout
resistance.Removetheneedle,maintainingcontrolovertheguidewire
atalltimes.NicktheskinwithaNo.11scalpelblade.
3. Withtheguidewireinplace,passthecentralcatheteroverthewireand
removetheguidewireafterthecatheterisinplace.Coverthecatheter
hubwithafingertopreventairembolization.
4. Attachasyringetothecatheterhubandensurethatthereisfreeback-
flowofdarkvenousblood.Attachthecathetertoanintravenousinfusion.
5. Securethecatheterinplacewith2-0silksutureandtape.Thecatheter
shouldbereplacedweeklyorifthereisanysignofinfection.
6. Obtainachestx-raytoconfirmpositionandruleoutpneumothorax.
IV. Internaljugularveincannulation.Theinternaljugularveinispositioned
behind the stemocleidomastoid muscle lateral to the carotid artery. The
cathetershouldbeplacedatalocationattheupperconfluenceofthetwo
belliesofthestemocleidomastoid,atthelevelofthecricoidcartilage.
CentralVenousCatheterization23
1. PlacethepatientinTrendelenburg'spositionandturnthepatient'shead
tothecontralateralside.
2. Choosealocationontherightorleft.Iflungfunctionissymmetricalandno
chesttubesareinplace,therightsideispreferredbecauseofthedirect
pathtothe superiorvenacava.PreparetheskinwithBetadinesolution
usingsteriletechniqueand placeadrape.Infiltratetheskinanddeeper
tissueswith1%lidocaine.
3. Palpatethecarotidartery.Usinga22-gaugescoutneedleandsyringe,
directtheneedlelateraltothecarotidarterytowardstheipsilateralnipple
ata30-degreeangletotheneck.Whileaspirating,advancetheneedle
untiltheveinislocatedandbloodflowsbackintothesyringe.
4. Remove the scout needle and advance a 16-gauge, thin wall catheter-
over-needlewithanattachedsyringealongthesamepathasthescout
needle.Whenbackflowofbloodisnotedintothesyringe,advancethe
catheterintothevein.Removetheneedleandconfirmbackflowofblood
throughthecatheterandintothesyringe.Removethesyringe,andusea
fingertocoverthecatheterhubtopreventairembolization.
5. Withthe16-gaugecatheterinposition,advancea0.89mmx45cmspring
guide wire through the catheter. The guidewire should advance easily
withoutresistance.
6. With the guidewire in position, remove the catheter and use a No. 11
scalpelbladetonicktheskin.
7. Placethecentralveincatheteroverthewire,holdingthewiresecureatall
times.Passthecatheterintothevein,removetheguidewire,andsuture
thecatheterwith0silksuture,tape,andconnectittoanIVinfusion.
8. Obtainachestx-raytoruleoutpneumothoraxandconfirmpositionofthe
catheter.
V. Subclavianveincannulation.Thesubclavianveinislocatedintheangle
formedbythemedial1/3oftheclavicleandthefirstrib.
1. Position the patient supine with a rolled towel located between the
patient'sscapulae,andturnthepatient'sheadtowardsthecontralateral
side.PreparetheareawithBetadineiodinesolution,and,usingsterile
technique,drapetheareaandinfiltrate1%lidocaineintotheskinand
tissues.
2. Advancethe16-gaugecatheter-over-needle,withsyringeattached,into
alocationinferiortothemid-pointoftheclavicle,untiltheclaviclebone
andneedlecomeincontact.
3. Slowly probe down with the needle until the needle slips under the
clavicle,andadvanceitslowlytowardstheveinuntilthecatheterneedle
enters the vein and a back flow of venous blood enters the syringe.
Removethesyringe,andcoverthecatheterhubwithafingertoprevent
airembolization.
4. With the 16-gauge catheter in position, advance a 0.89 mm x 45 cm
springguidewirethroughthecatheter.Theguidewireshouldadvance
easilywithoutresistance.
5. Withtheguidewireinposition,removethecatheter,anduseaNo.11
scalpelbladetonicktheskin.
6. Placethecentrallinecatheteroverthewire,holdingthewiresecureatall
times.Passthecatheterintothevein,andsuturethecatheterwith2-0
silksuture,tape,andconnecttoanIVinfusion.
7. Obtainachestx-raytoconfirmpositionandruleoutpneumothorax.
24PulmonaryArteryCatheterValues
VI. Pulmonaryarterycatheterization
1. Usingsteriletechnique,cannulateaveinusingthetechniqueabove.The
subclavianveinorinternaljugularveiniscommonlyused.
2. Advanceaguidewirethroughthecannula,thenremovethecannula,but
leavetheguidewireinplace.Keeptheguidewireundercontrolatall
times.Nicktheskinwithanumber11scalpelbladeadjacenttotheguide
wire,andpassanumber8Frenchintroduceroverthewireintothevein.
RemovethewireandconnecttheintroducertoanIVfluidinfusion,and
suturewith2-0silk.
3. Passtheproximalendofthepulmonaryarterycatheter(SwanGanz)to
anassistantforconnectiontoacontinuousflushtransducersystem.
4. Flush the distal and proximal ports with heparin solution, remove all
bubbles,andcheckballoonintegritybyinflating2ccofair.Checkthe
pressure transducer by quickly moving the distal tip and watching the
monitorforresponse.
5. Passthecatheterthroughtheintroducerintothevein,theninflatethe
balloonwith1.0ccofair,andadvancethecatheteruntiltheballoonisin
orneartherightatrium.
6. The approximate distance to the entrance of the right atrium is deter-
minedfromthesiteofinsertion:
Rightinternaljugularvein:10-15cm.
Subclavianvein:10cm.
Femoralvein:35.45cm.
7. Advancetheinflatedballoon,whilemonitoringpressuresandwaveforms
asthePAcatheterisadvanced.Advancethecatheterthroughtheright
ventricleintothemainpulmonaryarteryuntilthecatheterentersadistal
branch of the pulmonary artery and is stopped (as evidenced by a
pulmonarywedgepressurewaveform).
8. Do not advance the catheter while the balloon is deflated, and do not
withdrawthecatheterwiththeballooninflated.Afterplacement,obtaina
chestX-raytoensurethatthetipofcatheterisnofartherthan3-5cm
fromthemid-line,andnopneumothoraxispresent.
NormalPulmonaryArteryCatheterValues
Rightatrialpressure 1-7mmHg
RVPsystolic 15-25mmHg
RVPdiastolic 8-15mmHg
Pulmonaryarterypressure
PAPsystolic 15-25mmHg
PAPdiastolic 8-15mmHg
PAPmean 10-20mmHg
AcuteCoronarySyndromes25
Cardiovascular Disorders
RohamT.Zamanian,MD
FarhadMazdisnian,MD
MichaelKrutzik,MD
Acute Coronary Syndromes (Acute Myocardial
InfarctionandUnstableAngina)
Acutemyocardialinfarction(AMI)andunstableanginaarepartofaspectrum
known as the acute coronary syndromes (ACS), which have in common a
ruptured atheromatous plaque. These syndromes include unstable angina,
nonQ-waveMI,andQ-waveMI.TheECGpresentationofACSincludesST-
segmentelevationinfarction,ST-segmentdepression(includingnonQ-waveMI
andunstableangina),andnondiagnosticST-segment andT-waveabnormalities.
PatientswithST-segmentelevationwillusuallydevelopQ-waveMI.Patientswith
ischemicchestdiscomfortwhodonothaveST-segmentelevationwilldevelop
Q-waveMIandnonQ-waveMIorunstableangina.
I. Clinicalevaluationofchestpainandacutecoronarysyndromes
A.History.Chestpainispresentin69%ofpatientswithAMI.Thepainmay
becharacterizedasaconstricting orsqueezingsensationinthechest.
Paincanradiatetotheupperabdomen,back,eitherarm,eithershoulder,
neck,orjaw.AtypicalpainpresentationsinAMIincludepleuritic,sharpor
burningchestpain.Dyspnea,nausea,vomiting,palpitations,orsyncope
maybetheonlycomplaints.
B.Cardiac Risk factors include hypertension, hyperlipidemia, diabetes,
smoking,andastrongfamilyhistory(coronaryarterydiseaseinearlyor
mid-adulthoodinafirst-degreerelative).
C.Physicalexaminationmayrevealtachycardiaorbradycardia,hyper-or
hypotension, or tachypnea. Inspiratory rales and an S3 gallop are
associated with left-sided failure. Jugulovenous distention (JVD),
hepatojugularreflux,andperipheraledemasuggestright-sidedfailure.A
systolicmurmurmayindicateischemicmitralregurgitationorventricular
septaldefect.
II. Laboratoryevaluationofchestpainandacutecoronarysyndromes
A.Electrocardiogram (ECG). The initial ECG reveals diagnostic ST
elevations in only 40% of patients with a confirmed AMI. ST-segment
elevation(equaltoorgreaterthan1mV)intwoormorecontiguousleads
provides strong evidence of thrombotic coronary arterial occlusion and
makesthepatientacandidateforimmediatereperfusionbythrombolysis
orangioplasty.
B.Laboratorymarkers
1. Creatinephosphokinase(CPK) enzymeisfoundinthebrain,muscle,
and heart. The cardiac-specific dimer, CK-MB, however, is present
almostexclusivelyinmyocardium.
26AcuteCoronarySyndromes
CommonMarkersforAcuteMyocardialInfarction
Marker InitialEleva-
tionAfterMI
MeanTimeto
PeakEleva-
tions
TimetoRe-
turntoBase-
line
Myoglobin 1-4h 6-7h 18-24h
CTnl 3-12h 10-24h 3-10d
CTnT 3-12h 12-48h 5-14d
CKMB 4-12h 10-24h 48-72h
CKMBiso 2-6h 12h 38h
CTnI,CTnT=troponinsofcardiacmyofibrils;CPK-MB,MM=tissue
isoformsofcreatinekinase.
2. CK-MB subunits. Subunits of CK, CK-MB, -MM, and -BB, are
markersassociatedwithareleaseintothebloodfromdamagedcells.
ElevatedCK-MBenzymelevelsareobservedintheserum2-6hours
afterMI,butmaynotbedetecteduntilupto12hoursaftertheonset
ofsymptoms.
3. Cardiac-specifictroponinT(cTnT)isaqualitativeassayandcardiac
troponin I (cTnI) is a quantitative assay. The cTnT level remains
elevatedinserumupto14daysandcTnIfor3-7daysafterinfarction.
4. Myoglobin is the first cardiac enzyme to be released. It appears
earlierbutislessspecificforMIthanothermarkers.Myoglobinismost
usefulforrulingoutmyocardialinfarctioninthefirstfewhours.
III.Initialtreatmentofacutecoronarysyndromes
A. Continuous cardiac monitoring and IV access should be initiated.
Morphine, oxygen, nitroglycerin, and aspirin("MONA") should be
administeredtopatientswithischemic-typechestpainunlesscontraindi-
cated.
B. Morphine is indicated for continuing pain unresponsive to nitrates.
Morphine reduces ventricular preload and oxygen requirements by
venodilation.Administermorphinesulfate2-4mgIVevery5-10minutes
prnforpainoranxiety.
C. Oxygenshouldbeadministeredtoallpatientswithischemic-typechest
discomfortandsuspectedACSforatleast2to3hours.
D. Nitroglycerin
1. Nitroglycerin is an analgesic for ischemic-type chest discomfort.
Nitroglycerin is indicated for the initial management of pain and
ischemiaunlesscontraindicatedbyhypotension(SBP<90mmHg)or
RVinfarction.Continueduseofnitroglycerinbeyond48hoursisonly
indicatedforrecurrentanginaorpulmonarycongestion.
2. Initially,giveuptothreedosesof0.4mgsublingualNTGeveryfive
minutes or nitroglycerine aerosol, 1 spray sublingually every 5
minutes. An infusion of intravenous NTG may be started at 10-20
mcg/min, titrating upward by 5-10 mcg/min every 5-10 minutes
AcuteCoronarySyndromes27
(maximum, 3 mcg/kg/min). Titrate to decrease the mean arterial
pressureby10%innormotensivepatientsandby30%inthosewith
hypertension.SloworstoptheinfusioniftheSBPdropsbelow100
mmHg.
E. Aspirin
1. Aspirin should be given as soon as possible to all patients with
suspected ACS unless the patient is allergicto it. Aspirin therapy
reducesmortalityafterMIby25%.
2. Adoseof160-325mgofaspirinshouldbechewedandswallowedon
day1andcontinuedPOdailythereafter.Ifaspiriniscontraindicated,
clopidogrel(Plavix)75mgqdshouldbeadministered.
IV. Riskstratification,initialtherapy,andevaluationforreperfusionin
theemergencydepartment
RiskStratificationwiththeFirst12-LeadECG
Usethe12-leadECGtotriagepatientsinto1of3groups:
1. ST-segmentelevation
2. ST-segmentdepression($1mm)
3. NondiagnosticornormalECG
A. Patientswithischemic-typechestpainandST-segmentelevation$1mm
in 2 contiguous leads have acute myocardial infarction. Reperfusion
therapywiththrombolyticsorangioplastyisrecommended.
B. Patients with ischemic-type pain but normal or nondiagnosticECGs or
ECGsconsistentwithischemia(ST-segmentdepressiononly)usuallydo
nothaveAMI.Thesepatientsshouldnotbegivenfibrinolytictherapy.
C. PatientswithnormalornondiagnosticECGsusuallydonothaveAMI,and
theyshouldbeevaluatedwithserialcardiacenzymesandadditionaltests
todeterminethecauseoftheirsymptoms.
V. ManagementofST-segmentelevationmyocardialinfarction
A. PatientswithST-segmentelevationhaveAMIshouldreceivereperfusion
therapywithfibrinolyticsorpercutaneouscoronaryintervention.
B. Reperfusiontherapy:Fibrinolytics
1. PatientswhopresentwithischemicpainandST-segmentelevation($1
mmin$2contiguousleads)within12hoursofonsetofpersistentpain
shouldreceivefibrinolytic therapyunlesscontraindicated.Patientswith
a new bundle branch block (obscuring ST-segment analysis) and
history suggesting acute MI should also receive fibrinolytics or
angioplasty.
28AcuteCoronarySyndromes
TreatmentRecommendationsforAMI
SupportiveCareforChestPain
Allpatientsshouldreceivesupplementaloxygen,2L/minbynasalcanula,fora
minimumofthreehours
Twolarge-boreIVsshouldbeplaced
Aspirin:
Inclusion ClinicalsymptomsorsuspicionofAMI
Exclusion Aspirinallergy,activeGIbleeding
Recommendation Chewandswallowonedoseof160-325mg,thenorallyqd
Thrombolytics:
Heparin:
Inclusion
Exclusion
Recommendation
AllpatientswithischemicpainandST-segmentelevation($
1mmin$2contiguousleads)within12hoursofonsetof
persistentpain,age<75years.
Allpatientswithanewbundlebranchblockandhistory
suggestingacuteMI.
Activeinternalbleeding;historyofcerebrovascularacci-
dent;recentintracranialorintraspinalsurgeryortrauma;
intracranialneoplasm,arteriovenousmalformation,oraneu-
rysm;knownbleedingdiathesis;severeuncontrolledhyper-
tension
Reteplase(Retavase)10UIVPover2minx2.Givesec-
onddoseof10U30minafterfirstdoseOR
Tenecteplase(TNKase):<60kg:30mgIVP;60-69kg:35
mgIVP;70-79kg:40mgIVP;80-89kg:45mgIVP;$90kg:
50mgIVPOR
t-PA(Alteplase,Activase)15mgIVover2minutes,then
0.75mg/kg(max50mg)IVover30min,followedby0.5
mg/kg(max35mg)IVover30min.
Inclusion
Exclusion
Recommendation
Administerconcurrentlywiththrombolysis
ActiveinternalorCNSbleeding
Heparin60U/kgIVP,followedby12U/kg/hrcontinuousIV
infusionx48hours.MaintainaPTT50-70seconds
AcuteCoronarySyndromes29
Beta-Blockade:
Inclusion AllpatientswiththediagnosisofAMI.Within12hoursof
diagnosisofAMI
Exclusion SevereCOPD,hypotension,bradycardia,AVblock,pulmo-
naryedema,cardiogenicshock
Recommendation Metoprolol(Lopressor),5mgIVpushevery5minutesfor
threedoses;followedby25mgPObid.Titrateupto100
mgPObidOR
Atenolol(Tenormin),5mgIV,repeatedin5minutes,fol-
lowedby50-100mgPOqd.
Nitrates:
ACEInhibitors:
Inclusion
Exclusion
Recommendation
Allpatientswithischemic-typechestpain
Nitrateallergy;sildenafil(Viagra)withinprior24hours;
hypotension;cautioninrightventricularinfarction
0.4mgNTGinitiallyq5minutes,upto3dosesornitroglyc-
erineaerosol,1spraysublinguallyevery5minutes.IV
infusionofNTGat10-20mcg/min,titratingupwardby5-10
mcg/minq5-10minutes(max3mcg/kg/min).Sloworstop
infusionifsystolicBP<90mmHg
Inclusion
Exclusion
Recommendation
AllpatientswiththediagnosisofAMI.Initiatetreatment
within24hoursafterAMI
Bilateralrenalarterystenosis,angioedemacausedby
previoustreatment
Lisinopril(Prinivil)2.5-5mgqd,titrateto10-20mgqd.
MaintainsystolicBP>100mmhg
C. Thrombolytics
1. ECGcriteriaforthrombolysis
a. STElevation(>1mmintwoormorecontiguousleads),timeto
therapy12hoursorless,ageyoungerthan75years.
b. Anewbundlebranchblock(obscuringST-segmentanalysis)and
historysuggestingacuteMI.
2. Alteplase (t-PA, tissue-plasminogen activator, Activase) and
Reteplase(Retavase)convertplasminogentoplasmin.Bothagents
areclot-specific andbindtonewthrombus.Activaseissuperiorto
streptokinase.Thealteplasethirty-daymortalityrateof6.3%isthe
lowest of the fibrinolytics, compared with 7.3% for streptokinase.
Alteplaseprovidestheearliestandmostcompletereperfusion.
3. Streptokinase (SK, Streptase) provides greater benefit in older
patients with a smaller amount of myocardiumat risk who present
laterandthosewithagreaterriskofICH. ThedoseofIVSKis1.5
millionunitsgivenover60minutes.
D. Reperfusiontherapy:Percutaneouscoronaryintervention
30AcuteCoronarySyndromes
1. PCI is preferable to thrombolytic therapy if performed in a timely
fashionbyindividualsskilledintheprocedure.Coronaryangioplasty
provideshigherratesofflowthanthrombolyticsandisassociatedwith
lowerratesofreocclusionandpostinfarctionischemiathanfibrinolytic
therapy.
2. PatientsathighriskformortalityorsevereLVdysfunctionwithsigns
ofshock,pulmonary congestion, heartrate>100bpm,andSBP<100
mm Hg should be sent to facilitiescapable of performing cardiac
catheterizationandrapidrevascularization.Whenavailablewithin90
minutes,PCIisrecommendedforallpatients,particularlythosewho
haveahighriskofbleedingwithfibrinolytictherapy.
E. Heparinisrecommendedinpatientsreceivingselectivefibrinolyticagents
(tPA/Reteplase/tenectaplase). A bolus dose of 60 U/kg should be
followedbyinfusionatarateof12U/kg/hour(amaximumbolusof4000
U/kgandinfusionof1000U/hforpatientsweighing<70kg).AnaPTTof
50to70secondsisoptimal.
F. Beta-blockade use during and after AMI reduces mortality by 36%.
Contraindications to beta-blockers include severe LV failure and
pulmonaryedema,bradycardia(heartrate<60bpm),hypotension(SBP
<100mmHg),signsofpoorperipheralperfusion,second-orthird-degree
heartblock.
1. Metoprolol (Lopressor), 5 mg IV push every 5 minutes for three
doses;followedby25mgPObid.Titrateupto100mgPObidOR
2. Atenolol(Tenormin),5mgIV,repeatedin 5minutes,followedby50-
100mgPOqd.
G.ACE-inhibitors increase survival in patients with AMI. ACE-inhibitors
shouldbestartedbetween6to24hoursafterAMIandcontinuedfor4-6
weeks,andindefinitelyifejectionfraction<40%.
1. Captopril(Capoten)isgivenasa6.25mginitialdoseandtitratedup
to50mgpobid,or
2. Lisinopril(Prinivil)maybegivenas2.5-5mgqd,titrateto10-20mg
qd.
VI. Management NonQ-waveMIandhigh-riskunstableanginawithST-
segmentdepression.
A. NonQ-wave MI and unstable angina present with ST-segment
depression. Among patients with ST-segmentdepression, fibrinolytic
therapyprovidesnobenefit. Fibrinolytictherapyshouldnotbeusedin
patientswithST-segmentdepressionornondiagnosticECGs.
B. Aspirin(325mgqd)andheparin,60U/kgIVP,followedby12U/kg/hr
continuousIVinfusionx48hours(aPTT50-70seconds)shouldbegiven
to patients with ST-segment depression or T-wave inversion with
ischemic-typechestpain.
AcuteCoronarySyndromes31
HeparinandST-SegmentDepressionandNonQ-WaveMI/Unstable
Angina
! IVheparintherapyfor3to5daysisstandardforhigh-riskandsome
intermediate-riskpatients.Treatfor48hours,thenindividualized
therapy.
! LMWHisanacceptablealternativetoIVunfractionatedheparin.
-Enoxaparin(Lovenox)1.0mg/kgSQq12hOR
-Dalteparin(Fragmin)120IU/kg(max10,000U)SQq12h.
C. Nitratesshouldbegivenforrecurrentangina.Sublingualnitroglycerin
(NTG),initially,giveuptothreedosesof0.4mgsublingualNTGevery
five minutes or nitroglycerine aerosol, 1 spray sublingually every 5
minutes.Nitroglycerinpatch0.2mg/hrqd.Allowfornitrate-freeperiodto
prevent tachyphylaxis. Isosorbide dinitrate (Isordil) 10-60 mg PO tid -
[5,10,20,30,40mg],orisosorbidemononitrate(Imdur)30-60mgqd.
D. Beta-blockers.Abeta-blockershouldbeinitiatedforpatientswithST-
segmentdepression.
1.Beta-blockers reduce the size of the infarct in patientswho do not
receive fibrinolytic therapy. A significant decrease in death and
nonfatalinfarctionhasbeenobservedinpatientstreatedwithbeta-
blockersafterinfarction.Contraindicationstobeta-blockers:severeLV
failure and pulmonary edema, bradycardia (heart rate <60 bpm),
hypotension(SBP<100mmHg),signsofpoorperipheralperfusion,
second-orthird-degreeheartblock.
2.Metoprolol (Lopressor), 5 mg IV push every 5 minutes for three
doses;followedby25mgPObid.Titrateupto100mgPOOR
3.Atenolol(Tenormin),5mgIV,repeatedin5minutes,followedby50-
100mgPOqd.
E. Coronary angiography is recommended for high-risk patients with
recurrentischemia,depressedLVfunction,widespreadchangesonthe
ECG,orpriorMI.
F. GlycoproteinIIb/IIIainhibitors
1.TheGPIIb/IIIareceptorblockersreduceplateletaggregation.TheGP
IIb/IIIa inhibitors should be used for patients with non-ST-segment
elevationMI or high-risk unstable angina. These agents should be
usedwithaspirinorclopidogrelandunfractionatedheparin.Thedose
ofunfractionatedheparinshouldbereducedbyawhencombined
withGPblockers.
2.IntravenousGPblockerdosages
a. Abciximab (ReoPro), 0.25 mg/kg IVP over 2 min, then 0.125
mcg/kg/min(max10mcg/min)for12hours.
b. Eptifibatide (Integrilin), 180 mcg/kg IVP over 2 min, then 2
mcg/kg/minfor24-72hours.Use0.5mcg/kg/minifcreatinineis
>2.0mg/dL.
c. Tirofiban (Aggrastat), 0.4 mcg/kg/min for 30 min, then 0.1
mcg/kg/minIVinfusionfor24-72hours.Reducedosageby50%if
thecreatineclearanceis<30mL/min.
32AcuteCoronarySyndromes
VII. ManagementofpatientswithanondiagnosticECG
HeartFailure33
A. PatientswithanondiagnosticECGwhohaveanindeterminateoralow
riskofMIshouldreceiveaspirinwhileundergoingserialcardiacenzyme
studiesandrepeatECGs.
B. Treadmill stress testing should be considered for patients with a
suspicionofcoronaryischemia.
HeartFailure
Congestiveheartfailure(CHF)isdefinedastheinabilityofthehearttomeetthe
metabolicandnutritionaldemandsofthebody.Approximately75%ofpatients
withheartfailureareolderthan65-70yearsofage.Approximately8%ofpatients
betweentheagesof75and86haveheartfailure.
I. Etiology
A. ThemostcommoncausesofCHFarecoronaryarterydisease,hyperten-
sion, and alcoholic cardiomyopathy. Valvular diseases such as aortic
stenosisandmitralregurgitation,arealsocommon.
B. Coronary artery disease is the etiology of heart failure in two-thirds of
patientswithleftventriculardysfunction.Heartfailureshouldbepresumed
tobeofischemicoriginuntilprovenotherwise.
II. Clinicalpresentation
A. Leftheartfailureproducesdyspneaandfatigue.Rightheartfailureleads
tolowerextremityedema,ascites,congestivehepatomegaly,andjugular
venousdistension.Symptomsofpulmonarycongestionincludedyspnea,
orthopnea, and paroxysmal nocturnal dyspnea. Clinical impairment is
causedbyleftventricularsystolicdysfunction(ejectionfractionoflessthan
40%)in80-90%ofpatientswithCHF.
B. Patientsshouldbeevaluatedforcoronaryarterydisease,hypertension,
and valvular dysfunction. Use of alcohol, chemotherapeutic agents
(daunorubicin),negativeinotropicagents,andsymptomsofarecentviral
syndromeshouldbeassessed.
C. CHFcanpresentwithshortnessofbreath,dyspneaonexertion,paroxys-
mal nocturnal dyspnea, orthopnea, nocturia, and cough. Exertional
dyspneaisextremelycommoninpatientswithheartfailure.
PrecipitantsofCongestiveHeartFailure
Myocardialischemiaorinfarc-
tion
Atrialfibrillation
Worseningvalvulardisease
Pulmonaryembolism
Hypoxia
Severe,uncontrolledhyperten-
sion
Thyroiddisease
Pregnancy
Anemia
Infection
Tachycardiaorbradycardia
Alcoholabuse
Medicationordietarynoncompli-
ance
D. Physicalexamination.Lidlag,goiter,medicationuse,murmurs,abnormal
heartrhythmsmaysuggestatreatableunderlyingdisease.Patientswith
CHFmaypresentwithrestingtachycardia,jugularvenousdistension,a
thirdheartsound,rales,lowerextremityedema,oralaterallydisplaced
34HeartFailure
apicalimpulse.Poorcapillaryrefill,coolextremities,oranalteredlevelof
consciousnessmayalsobepresent.
NewYorkHeartAssociationCriteriaforHeartFailure
ClassI Asymptomatic
ClassII Symptomswithmoderateactivity
ClassIII Symptomswithminimalactivity
ClassIV Symptomsatrest
E. Laboratoryassessment
1. Patients with symptoms suggestive of CHF should have a 12-lead
ECG.
2. Impedance cardiography (ICG) is a noninvasive, reliable method of
measuringcardiacindexandstrokevolume.Itshouldbedoneonthe
first dayofhospitalizationandrepeatedtoassessresponsetodrug
therapy.
3. A chest x-ray should be performed to identify pleural effusions,
pneumothorax,pulmonaryedema,orinfiltrates.
4. Ifcardiacischemiaorinfarctionissuspected,cardiacenzymesshould
bedrawn.Acompletebloodcount,electrolytes,anddigoxinlevel,if
applicable, also are mandatory. Patients with suspected hyper-
thyroidismshouldhavethyroidfunctionstudiesdrawn.
F. Echocardiography is recommended to evaluate the presence of
pericardial effusion, tamponade, valvular regurgitation, wall motion
abnormalities,andejectionfraction.
LaboratoryWorkupforSuspectedHeartFailure
Bloodureanitrogen
Cardiacenzymes(CK-MB,
troponin,orboth)
Completebloodcellcount
Creatinine
Electrolytes
Liverfunctiontests
Magnesium
Thyroid-stimulatinghormone
Urinalysis
Echocardiogram
Electrocardiography
Impedancecardiography
III. Managementofchronicheartfailure
A. Patientsshouldalsobeplacedonoxygentomaintainadequateoxygen
saturation. In patients with severe symptoms (ie, pulmonary edema),
continuouspositiveairwaypressure(CPAP)orendotrachealintubation
(ETI)maybeemployed.
B. Angiotensin-convertingenzymeinhibitorssignificantlyreducemorbidity
andmortalityinCHF.Sideeffectsincludecough,worseningrenal function,
hyperkalemia,hypotension,andtheriskofangioedema.ACEIsshouldbe
startedataverylowdoseandtitratedupgraduallytorelieveshortnessof
breath.Renalfunctionandelectrolytesshouldbemonitored.
HeartFailure35
ACEInhibitorsUsedforHeartFailure
Benazepril(Lotensin) start10mgpobid,target20-40mgpobid
Captopril(Capoten)start6.25-12.5mgpotid,targetdose50-100mgtid
Enalapril(Vasotec)start2.5mgpoqd/bid,target2.5-10mgtid
Fosinopril(Monopril)start10mgpoqd,target20-40mg/d
Lisinopril(Prinivil,Zestril)start5mgpoqd,target5-20mg/d
Quinapril(Accupril)start5mgpobid,target20-40mg/d
Ramipril(Altace)start2.5mgpobid,target10mg/d
Trandolapril(Mavik)start1mgpoqd,target2-4mgqd
C. AngiotensinIIreceptorblockers(ARBs).Inpatientswhocannottolerate
orhavecontraindicationstoACEinhibitors,ARBsshouldbeconsidered.
ARBsareaseffectiveasACEinhibitorswithalowerincidenceofcough
andangioedema.
AngiotensinIIReceptorBlockersforHeartFailure
Candesartan(Atacand)start4-8mgqdbid,target8-16mgqdbid
Irbesartan(Avapro)start75-150mgqd,target150-300mgqd
Losartan(Cozaar)start25-50mgqd,target50mgbid
Valsartan(Diovan)start80mgqd,target160-320mgqd
D. Hydralazine/Isordil combination may be used in patients who are
intoleranttoACE-inhibitorsandARBs;however,thiscombinationisless
effectiveinreducingmortality.Hydralazinecancausereflextachycardia
andincreaseischemicpain.Reflex tachycardiaduetohydralazinemaybe
beneficial in patients with bradycardia caused by beta-blockers. The
dosageofhydralazineis10-50mgqid,combinedwithisosorbidedinitrate
(Isordil)10-40mgqid,ORisordilmononitrate(Imdur)30-60mgqd.
E. Diureticsinduceperipheralvasodilation,reducecardiacfillingpressures,
andpreventfluidretention.Loopdiureticsarethemostpotentagentsin
CHF. Diuretics should be prescribed for patients with heart failure who
havevolumeoverload.
DiureticTherapyinCongestiveHeartFailure
Loopdiuretics
Furosemide(Lasix)20-200mgIV/POdailyorbid,or10-20mg/hrIV
infusion
Bumetanide(Bumex)0.5-4.0mgIV/POdailyorbid
Torsemide(Demadex)5-100mgIV/POdaily
Long-actingthiazidediuretics
Metolazone(Zaroxolyn)2.5-10.0mgqdPObid
Hydrochlorothiazide25POmgqd
AldosteroneAntagonists
Spironolactone(Aldactone)12.5-25mgPOqd
F. Beta-Blockersarebeneficialinheartfailure,improvingcontractilityand
survival. Beta-blockers should be started at low doses and advanced
36HeartFailure
slowly. Beta-blockersshouldnotbeusedinacutepulmonaryedemaor
decompensated heart failure, and they should only be initiated in the
stable patient. Beta-blockers are an add-on therapy for patients being
treatedwithACEinhibitors.
Carvedilol,Metoprolol,andBisoprololDosagesandSideEffects
Carvedilol(Coreg)startat1.625-3.125mgbid;targetdose25-50mg
bid
Metoprolol(Lopressor)startat12.5mgbid;targetdose100mgbid
Bisoprolol(Zebeta)startat1.25mgqd;targetdose10mgqd
DigoxinDosing
Startat0.250mg/dwithnearnormalrenalfunction;startat0.125mg/d
ifrenalfunctionimpaired.
Maintainserumdigoxinlevelof0.8-1.2ng/mL.
G. Digoxin does not improve survival in CHF (as do ACE-inhibitors and
beta-blockers).Digoxin maybeaddedtoaregimenofACE-inhibitorsand
diuretics if symptoms of heart failure persist. Digoxin can increase
exercise tolerance, improve symptoms, and decrease the risk of
hospitalization.
H. SpironolactoneimprovesmortalityinsevereCHFandshouldbeused
inadditiontoanACE-inhibitororARB.Adosageof25mgqdshouldbe
consideredinpatientswithsevereCHF.Itcancausehyperkalemia,rash,
andgynecomastia.
I. Nonpharmacologictreatments
1. Salt restriction (a diet with 2 g sodium or less), alcohol restriction,
waterrestrictionforpatientswithsevererenalimpairment,andregular
aerobicexerciseastolerated.
2. Synchronizedbiventricularpacinginpatientswithanejectionfraction
of<40%andwideQRSdurationof>150msecmayimprovesymp-
tomsandtheoverallclinicalcourse.
J. Inotropicsupport
1. Positiveinotropicagentsimprovequalityoflifeandreduceneedfor
hospitalizationbutincreasemortality.Parenterallypositiveinotropic
therapy increases cardiac output and decreases symptoms of
congestion.
2. Parenteral inotropic agents can be administered continuously in
patients with exacerbations of heart failure. These agents may be
administered continuously or intermittently at home. Impedance
cardiographyisusedtoassessclinicalresponsebeforeandduring
treatment.
AtrialFibrillation37
InotropicAgentsforCardiogenicShock
Milrinone(Primacor)startat0.375mcg/kg/minandtitrateto0.75
mcg/kg/min
Dobutamine(Dobutrex)startat2-3mcg/kg/minandtitrate5
mcg/kg/min
Dopamine(Intropin)startat2-5mcg/kg/minandtitrateto10
mcg/kg/min
K. Natriureticpeptides
1. Atrialandbrainnatriuretic peptidesregulatecardiovascularhomeosta-
sisandfluidvolume.
2. Nesiritide(Natrecor)isstructurallysimilartoatrialnatriureticpeptide.
It has natriuretic, diuretic, vasodilatory, smooth-muscle relaxant
properties, and inhibits the renin-angiotensin system. Nesiritide is
indicatedforthetreatmentofmoderate-to-severeheartfailure.
3. The initial dose of nesiritide is 0.015 mcg/kg/min IV infusion slowly
titratedtomax0.03mcg/kg/min.Hypotensionoccursfrequentlywitha
mildincreaseinheartrate.
TreatmentofAcuteHeartFailure/PulmonaryEdema
Oxygentherapy,2L/minbynasalcanula
Furosemide(Lasix)20-80mgIV(patientsalreadyonoutpatientdose
mayrequiremore)
Nitroglycerinestartat10-20mcg/minandtitratetoBP(usewithcau-
tionifinferior/rightventricularinfarctionsuspected)
Sublingualnitroglycerin0.4mg
Morphinesulfate2-4mgIV.AvoidifinferiorwallMIsuspectedorif
hypotensiveorpresenceoftenuousairway
Potassiumsupplementationprn
AtrialFibrillation
Atrialfibrillation(AF)isthemostcommonarrhythmia.Themedianageofonset
is 75, and the incidence and prevalence increase dramatically with age. For
patientsolderthan80years,theincidenceofAFis9%.Forpatientsaged80-90,
nearlyone-thirdofstrokesthatoccurarerelatedtoAF.
I. Pathophysiology.Thecardiacconditionsmostcommonlyassociatedwith
AFarecoronaryarterydisease,hypertension,rheumaticheartdisease,mitral
valvedisease,cardiomyopathies,andopen-heartsurgery.Hypertensionand
coronaryarterydiseasearethemostfrequentrisk factors,accountingfor65%
ofAFcases.Themostcommonnoncardiaccausesarepulmonarydiseases
(includingCOPD),hypoxia,andhyperthyroidism.
II. Clinicalevaluation
38AtrialFibrillation
A. Patients with AF often experience dyspnea and palpitations, although
somemaybe asymptomatic.AFmaybeassociatedwithpalpitations,
dizziness,dyspnea,chestpain,syncope,fatigue,orconfusion.
B. The most common physical sign of AF is an irregular pulse. Other
physical exam findings include a pulse deficit, absent a wave in the
jugularvenouspulse,andavariableintensityofthefirstheartsound.
CausesofAtrialFibrillation
StructuralHeartDisease AbsenceofStructuralHeartDisease
Hypertension
Ischemicheartdisease
Valvularheartdisease:Mitralstenosis,
aorticstenosis,mitralregurgitation
Pericarditis
Cardiactumors
Sicksinussyndrome
Cardiomyopathies
Congenitalheartdisease
Wolf-Parkinson-Whitesyndrome
Pulmonarydiseases:COPD,hypoxia,
pneumonia,pulmonaryembolus,
metabolicdisorders,thyrotoxicosis,
electrolyteimbalance
Acuteethanolintoxication
Methylxanthinederivatives:
Theophylline,caffeine
SystemicillnessSepsis,malignancy
Loneatrialfibrillation
III. Diagnosticstudies
A. Laboratory studies should include chemistries, CBC, INR/PTT, and a
TSH. A chest x-ray may uncover COPD, pneumonia, CHF, or
cardiomegaly.
B. Ambulatory 24-hour (Holter) ECG monitoring should be performed to
determineboththefrequencyanddurationofAF.
C. Echocardiogramprovidesinformationoncardiacdimensions(leftatrial
size),LVsystolicfunction,valvulardisease,andLVhypertrophy.
IV. Initialmanagement
A. If the duration of AF is less than 48 hours, the initial goals are either
cardioversionorventricularratecontrolandobservation.Ifthepatientis
nothemodynamicallycompromisedandtheAFisofnewonset,aninitial
period of observation using medications for rate control and
anticoagulation with heparin are initiated. If AF persists despite rate
control, restoration of sinus rhythm is the usual goal if the patient is
symptomatic during AF, requires AV synchrony for improved cardiac
output,orwantstoavoidlifelonganticoagulation.Sinusrhythmcanbe
achieved with either external cardioversion and/or pharmacological
agents.
B. Initialtreatmentofatrialfibrillation
1. AnticoagulationinpatientswithnonvalvularAFreducestheincidence
ofembolicstrokes.
2. Oralanticoagulationtherapywithwarfarin(Coumadin),withanINR
goalbetween2.0-3.0,shouldbeconsideredin allAFpatientswith
oneormoreriskfactors,asdescribedbelow,regardlessofage.
3. Inpatientswithoutrheumaticheartdiseasewhoareyoungerthan75
yearsofage,warfarintherapyshouldbeinitiatedifrisk factors are
present, including previous transient ischemic attack or stroke,
hypertension,heartfailure,diabetes,clinicalcoronaryarterydisease,
mitralstenosis,prostheticheartvalves,orthyrotoxicosis.Inpatients
AtrialFibrillation39
younger than 65 and without these risk factors (lone AF), aspirin
alonemaybeappropriateforstrokeprevention.
4. Patients between the ages of 65 and 75 with none of these risk
factorscouldbetreatedwitheitherwarfarinoraspirin.
5. Inpatientsolderthan75withAF,oralanticoagulationwithwarfarinis
recommended. In patients with major contraindications to warfarin
(intracranial hemorrhage, unstable gait, falls, syncope, or poor
compliance),adailyaspirinisareasonablealternative.
6. If the duration of AF is unknown or more than 48 hours, then rate
control and anticoagulation therapy should be initiated first. The
patient should be evaluated for the presence of an intracardiac
thrombuswithatransesophagealechocardiography(TEE).IftheTEE
demonstrates a clot, the patient is anticoagulated for three weeks
before a scheduled cardioversion. If no left atrial thrombus is
identifiedbyTEE,heparinisstartedandthepatientiscardioverted.
Followingsuccessfulcardioversion,thepatientisplacedonwarfarin
foranadditionalfourweeks.
C. Ratecontrol
1. PatientswithAFofgreaterthanoneyeardurationoraleftatrialsize
greaterthan50mmmayhavedifficultyinconvertingtosinusrhythm.
Inthesepatients,ratecontrol,ratherthanconversiontosinusrhythm
may,bebeneficial.AcontrolledventricularrateinAFislessthan90
bpmatrest.
2. Thepharmacologicalagentsusedforratecontrolarecalciumchannel
blockers(diltiazem,verapamil),beta-blockers(metoprolol,esmolol)
anddigoxin.Calciumchannelblockersshouldbeusedfirstbecause
ofrapidonsetofactioncomparedtodigoxin,whichtakes4-6hours
toshowpharmacologicaleffect.Digoxinisthefirstdrugofchoicein
significantleftventriculardysfunction.
3. CalciumchannelblockerscanslowAVnodeconductionandare
first-lineagentsforratecontroltherapy.
4. Beta-blockersslowAVnodalandsinoatrialnodalconduction.The
mostcommonlyusedbeta-blockersaremetoprololandatenolol.
5. Digoxin has numerous drug interactions, an unpredictable dose
responsecurve,andapotentiallylethaltoxicity.Digoxinisisreserved
forpatientswithsystolicdysfunctionandheartfailure.
AgentsUsedforHeartRateControlinAtrialFibrillation
Agent Loading
Dose
OnsetofAc-
tion
Maintenance
Dosage
MajorSide
Effects
Diltiazem
(Cardizem)
0.25mgper
kgIVover2
minutes,may
repeatdose
with0.35
mg/kgafter15
minx1
2-7minutes 5-15mgper
hourIVor120-
360mgPOev-
erydayindiv-
ideddoses
Hypotension,
heartblock,
heartfailure
Verapamil
(Calan,
Isoptin)
0.075-0.15mg
perkgIVover
2minutes
3-5minutes 240-360mgPO
everydayin
divideddoses
Hypotension,
heartblock,
heartfailure
40AtrialFibrillation
Agent Loading
Dose
OnsetofAc-
tion
Maintenance
Dosage
MajorSide
Effects
Esmolol
(Brevibloc)
0.5mgperkg
IVoverone
minute
5minutes 0.05-0.2
mg/kg/minute
IV
Hypotension,
heartblock,
bradycardia,
asthma,heart
failure
Metoprolol
(Lopressor)
2.5-5mgIV
bolusover2
minutes,upto
3doses
5minutes 50-200mgPO
everydayin2
dailydoses
Hypotension,
heartblock,
bradycardia,
asthma,heart
failure
Propranolol
(Inderal)
0.15mgper
kg
5minutes 40-320mgPO
everydayin
divideddoses
Hypotension,
heartblock,
bradycardia,
asthma,heart
failure
Digoxin
(Lanoxin)
0.25mgIVor
POevery4
hours,upto
1.0-1.5mg
4-6hours 0.125-0.25mg
PO/IVqd
Digitalistoxic-
ity,heart
block,brady-
cardia,ven-
tricularfibrilla-
tion
AgentsUsedforHeartRateControlinAtrialFibrillation
Drug Mechanism
ofAction
ECG
Changes
Dose AdverseRe-
action
ClasslaAgents
Quinidine DecreaseNa
influx
Reduce
upstroke
velocity,
Prolong
repolariza-
tion
QRSwid-
ens,QT
lengthens
Sulfate300-600
mgpoq6-8hrs
Quinaglute324-
628mgpoq8-
12hrs
GI,cinchonism
VT/VF/
Torsadede
Pointes
Procain-
amide
QRSwid-
ens,QT
lengthens
Load:IV13-17
mg/kgover30-
60min
Maintenance:IV
2-4mg/minor
ProcanSR750-
1500mgpo
q6hr
SLE-likesyn-
drome,confu-
sion
AtrialFibrillation41
ClassIcAgents
Flecainide Reductionin
upstroke
velocity
QRSwid-
ens,QT
lengthens
Start50-100mg
poq12hr;max.
200bid
Dizziness,
headaches
Propa-
fenone
QRSwid-
ens,QT
lengthens
Start150mgpo
q8hrs;max.300
mgpoq8hr
Drymouth,GI,
dizziness
ClassIIIAgents
Amio-
darone
BlocksK
efflux,pro-
longs
repolar-
ization
Dose-
depend-
antQT
prolonga-
tion
Load400mgpo
tidx7-14days,
then400mgpo
qdx1month;
Maintenance:
100-400mg/day
Ataxia,trem-
orspulmonary
fibrosis,pneu-
mon-
itis/alveolitis,
skindiscolor-
ation,thyroid
andLFT
abnormalities
Sotalol Potentbeta-
blockingac-
tivity
80mgpobid;
max.160mgbid
Bradycardia,
Torsadede
Pointes.
Ibutilide Prolongac-
tionpotential
andrefrac-
toryperiod
1mgIVinfusion
over10min,
mayrepeatonce
after10min
Torsadein3-
8%
Dofetilide 125-500mcg
bid,depending
onrenalfunction
0.5-10%tor-
sade
D. Antiarrhythmics.Restorationofsinusrhythmistheoptimalgoal,asit
mayrelievesymptomsandimprovecardiacoutput.
1. Class Ia. These medications act by blocking the fast sodium
channel,reducingtheimpulseconductionthroughthemyocardium.
a. Quinidine can be used for acute conversion as well as to
maintainofsinusrhythm.
b. Procainamidecanalsobeusedforbothacuteconversionand
maintenance.Itisslightlylesseffectivethanquinidine.
c. Disopyramidehasnegativeinotropicproperties.Disopyramide
is infrequentlyusedinthetreatmentofAFduetopoorefficacy
andfrequentsideeffects.
2. Class lc. This class of medications acts by prolonging
intraventricularconduction.
a. Flecainide can cause acute conversion to sinus rhythm in 50-
55%. Due to its negative inotropic action, flecainide should be
used cautiously in patients with AF and hypertrophic
cardiomyopathy.Itshouldnotbeusedinpatientswithstructural
42HypertensiveEmergency
heartdisease.ItisreservedforpatientswithnormalLVfunction
andrefractoryAF.
b. Propafenonemayhavefewersideeffectsandisbettertolerated
thantheIaagents.Itisavailableonlyinanoralformandcanalso
be given as a single bolus dose for AF of less than 24 hours.
Proarrhythmiacanoccurbutisreportedlessfrequentlythanwith
theotherIcmedications.Propafenoneisusefulforpatientswho
arehypertensiveandhaveastructurallynormalheartwithAF.
Propafenoneshouldbeavoidedinpatientswithstructuralheart
disease.
3. Class III. The medications in this class act by blocking outward
potassiumcurrents,resultinginincreasedmyocardialrefractoriness.
All class III agents cause a dose-dependent QTc prolongation,
resultinginTorsadesdePointes.Theseagentsarecontraindicated
iftheQTcis>0.44seconds.
a. Amiodarone (Cordarone) has sodium, calcium, and beta-
blockingeffects.Amiodaronehasalowproarrhythmiaprofile.Itis
safeandefficaciousinpatients withCHFandAF.Sideeffects
includepulmonaryfibrosis,pneumonitis,skindiscoloration,thyroid
andliverabnormalities,ataxia,andtremors(33%).
b. Sotalol(Betapace)hasabeta-blockingeffect.Itislesseffective
thanquinidine,withaconversionrateof20%.Itismostappropri-
ateforsinusmaintenanceinpatientswithAFandcoronaryartery
disease. Sotalol should be avoided in patients with severe LV
dysfunctionandCOPD.
c. Ibutilide(Corvert)ishighlyeffectivefortheconversionofrecent
onsetAF(30%)andatrialflutter(70%).Polymorphicventricular
tachycardiaoccursinabout6%.Pretreatmentwithmagnesium
maypreventpolymorphicventriculartachycardia.
d. Dofetilide (Tikosyn) is indicated for acute conversion and
maintenance of atrial fibrillation. The success rate in acute
conversionis30%.
E. Nonpharmacologic strategies. Due to drug intolerance, possible
proarrhythmic effects, and disappointing long-term efficacy of the
antiarrhythmicagents,non-pharmacologicaltherapieshaveanimportant
roleinthemanagementofAF.
1. Electricalcardioversionisrapidandhighlyeffective,withsuccess
ratesgreaterthan80%.
2. Radiofrequency catheter ablation/atrial defibrillators. The
deliveryofradiofrequencycurrentthroughacathetertipadvancedto
theatriumishighlyeffectiveandsafe.
HypertensiveEmergency
Hypertensivecrisesaresevereelevationsinbloodpressure(BP)characterized
byadiastolicbloodpressure(BP)higherthan120-130mmHg.
I. Clinicalevaluationofhypertensivecrises
A.Hypertensiveemergencyisdefinedbyadiastolicbloodpressure>120
mmHgassociatedwithongoingvasculardamage.Symptomsorsignsof
HypertensiveEmergency43
neurologic,cardiac,renal,orretinaldysfunctionarepresent.Hypertensive
emergenciesincludeseverehypertensioninthefollowingsettings:
1. Aorticdissection
2. Acuteleftventricularfailureandpulmonaryedema
3. Acuterenalfailureorworseningofchronicrenalfailure
4. Hypertensiveencephalopathy
5. Focalneurologicdamageindicatingthromboticorhemorrhagicstroke
6. Pheochromocytoma, cocaine overdose, or other hyperadrenergic
states
7. Unstableanginaormyocardialinfarction
8. Eclampsia
B.Hypertensiveurgencyisdefinedasdiastolicbloodpressure>120mm
Hgwithoutevidenceofvasculardamage;thedisorderisasymptomatic
andnoretinallesionsarepresent.
C.Causesofsecondaryhypertensioninclude renovascularhypertension,
pheochromocytoma, cocaine use, withdrawal from alpha-2 stimulants,
clonidine, beta-blockers or alcohol, and noncompliance with
antihypertensivemedications.
44HypertensiveEmergency
II. Initialassessmentofseverehypertension
A.Whenseverehypertensionisnoted,themeasurementshouldberepeated
inbotharmstodetectanysignificantdifferences.Peripheral pulsesshould
be assessed for absence or delay, which suggests dissecting aortic
dissection.Evidenceofpulmonaryedemashouldbesought.
B.Target organ damage is suggested by chest pain, neurologic signs,
altered mental status, profound headache, dyspnea, abdominal pain,
hematuria,focalneurologicsigns(paralysisorparesthesia),orhyperten-
siveretinopathy.
C.Prescription drug use should be assessed, including missed doses of
antihypertensives.Historyofrecentcocaineoramphetamineuseshould
besought.
D.If focal neurologic signs are present, a CT scan may be required to
differentiatehypertensiveencephalopathyfromastrokesyndrome.
III. Laboratoryevaluation
A.Completebloodcell count,urinalysisforprotein,glucose,andblood;urine
sedimentexamination;chemistrypanel(SMA-18).
B.Ifchestpainispresent,cardiacenzymesareobtained.
C.If the history suggests a hyperadrenergic state, the possibility of a
pheochromocytomashouldbeexcludedwitha24-hoururineforcatechol-
amines.Aurinedrugscreenmaybenecessarytoexcludeillicitdruguse.
D.Electrocardiogramshouldbecompleted.
E. Suspectedprimaryaldosteronismcanbeexcludedwitha24-hoururine
potassium and an assessment of plasma renin activity. Renal artery
stenosis can be excluded with captopril renography and intravenous
pyelography.
ScreeningTestsforSecondaryHypertension
RenovascularHyper-
tension
Captoprilrenography:Renalscanbeforeandafter25mg
PO
Intravenouspyelography
MRIangiography
Hyperaldosteronism Serumpotassium
24-hrurinepotassium
Plasmareninactivity
CTscanofadrenals
Pheochromocytoma 24-hrurinecatecholamines
CTscan
NuclearMIBGscan
Cushing'sSyndrome PlasmaACTH
Dexamethasonesuppressiontest
Hyperparathyroidism Serumcalcium
Serumparathyroidhormone
IV. Managementofhypertensiveemergencies
A.Thepatientshouldbehospitalizedforintravenousaccess,continuous
intra-arterial blood pressure monitoring, and electrocardiographic
monitoring. Volume status and urinary output should be monitored.
HypertensiveEmergency45
Rapid, uncontrolled reductions in blood pressure should be avoided
becausecoma,stroke,myocardialinfarction,acuterenalfailure,ordeath
mayresult.
B.Thegoalofinitialtherapyistoterminateongoingtargetorgandamage.
Themeanarterialpressureshouldbelowerednotmorethan20-25%,or
toadiastolicbloodpressureof100mmHgover15to30minutes.
V. Parenteralantihypertensiveagents
A.Nitroprusside(Nipride)
1. Nitroprussideis thedrugofchoiceinalmostallhypertensiveemergen-
cies(exceptmyocardialischemiaorrenalimpairment).Itdilatesboth
arteries and veins, and it reduces afterload and preload. Onset of
actionisnearlyinstantaneous,andtheeffectsdisappear1-2minutes
afterdiscontinuation.
2. The starting dosage is 0.25-0.5 mcg/kg/min by continuous infusion
witharangeof0.25-8.0mcg/kg/min.Titratedosetograduallyreduce
bloodpressureoverminutestohours.
3. Whentreatmentisprolongedorwhenrenalinsufficiencyispresent,
the risk of cyanide and thiocyanate toxicity is increased. Signs of
thiocyanatetoxicityincludeanorexia,disorientation,fatigue,hallucina-
tions,nausea,toxicpsychosis,andseizures.
B.Nitroglycerin
1. Nitroglycerinisthedrugofchoiceforhypertensiveemergencieswith
coronary ischemia. It should not be used with hypertensive
encephalopathybecauseitincreasesintracranialpressure.
2. Nitroglycerinincreasesvenouscapacitance,decreasesvenousreturn
andleftventricularfillingpressure.Ithasarapidonsetofactionof2-5
minutes.Tolerancemayoccurwithin24-48hours.
3. Thestartingdoseis15mcgIVbolus,then5-10mcg/min(50mgin
250mLD5W).Titratebyincreasingthedoseat3-to5-minuteinter-
valsuptomax1.0mcg/kg/min.
C.LabetalolIV(Normodyne)
1. Labetalol is a good choice if BP elevation is associated with
hyperadrenergic activity, aortic dissection, an aneurysm, or post-
operativehypertension.
2. Labetalol is administered as 20 mg slow IV over 2 min. Additional
dosesof20-80mgmaybeadministeredq5-10min,thenq3-4hprnor
0.5-2.0mg/minIVinfusion.Labetaloliscontraindicatedinobstructive
pulmonarydisease,CHF,orheartblockgreaterthanfirstdegree.
D.EnalaprilatIV(Vasotec)
1. Enalaprilatis anACE-inhibitorwitharapidonsetofaction(15min)and
long duration of action (11 hours). It is ideal for patients with heart
failureoraccelerated-malignanthypertension.
2. Initialdose,1.25mgIVP(over2-5min)q6h,thenincreaseupto5mg
q6h.Reducedoseinazotemicpatients.Contraindicatedinbilateral
renalarterystenosis.
E.Esmolol(Brevibloc)is anon-selectivebeta-blockerwitha1-2minonset
ofactionandshortdurationof10min.Thedoseis500mcg/kg/minx1
min,then50mcg/kg/min;max300mcg/kg/minIVinfusion.
F. Hydralazine is a preload and afterload reducing agent. It is ideal in
hypertensionduetoeclampsia.Reflextachycardiaiscommon.Thedose
is20mgIV/IMq4-6h.
46VentricularArrhythmias
G. Nicardipine(CardeneIV)isacalciumchannelblocker.Itiscontrain-
dicatedinpresenceofCHF.Tachycardiaandheadachearecommon.
Theonsetofactionis10min,andthedurationis2-4hours.Thedose
is5mg/hrcontinuousinfusion,upto15mg/hr.
H.Fenoldopam(Corlopam)isavasodilator.Itmaycausereflextachycar-
diaandheadaches.Theonsetofactionis2-3min,andthedurationis30
min. The dose is 0.01 mcg/kg/min IV infustion titrated, up to 0.3
mcg/kg/min.
I. Phentolamine(Regitine)isanintravenousalpha-adrenergicantagonist
used in excess catecholamine states, such as pheochromocytomas,
reboundhypertensionduetowithdrawalofclonidine,anddrugingestions.
Thedoseis2-5mgIVevery5to10minutes.
J. Trimethaphan(Arfonad)isaganglionic-blockingagent.Itisusefulin
dissecting aortic aneurysm when beta-blockers are contraindicated;
however,itisrarelyusedbecausemostphysiciansaremorefamiliarwith
nitroprusside.Thedosageoftrimethoprimis0.3-3mg/minIVinfusion.
VentricularArrhythmias
I. Ventricularfibrillationandtachycardia
-Ifunstable(seeACLSprotocolpage5),defibrillatewithunsynchronized
200J,300J,then360J.
-Oxygen100%bymask.
-Procainamide loading dose 10-15 mg/kg at 20 mg/min IV or 100 mg IV
q10min,then2-4mg/minIVmaintenanceOR
-Alsoseeotherantiarrhythmicsbelow.
II. TorsadesdePointes
-Correct underlying cause and consider discontinuing drugs that cause
TorsadesdePointes(dofetilide,ibutilide,sotalol,amiodarone,quinidine,
procainamide,disopyramide,moricizine,bepridil, phenothiazines,tricyclic
andtetracyclicantidepressants,vasopressin,imidazoles,pentamidine);
correcthypokalemiaandhypomagnesemia.
-Defibrillatewith360J.
-Magnesiumsulfate(drugofchoice),2gmIVpush.
-Isoproterenol(Isuprel)2-20:g/min(2mgin500mLD5W,4:g/mL)OR
-Phenytoin(Dilantin)100-300mgIVgivenin50mgincrementsq5min.
III. Otherantiarrhythmics
ClassIb
-Lidocaine50-100mg(1mg/kg)IV,then2-4mg/minIV.
-Mexiletine(Mexitil)100-200mgPOq8h,max1200mg/d.
-Tocainide(Tonocard)loading400-600mg PO,then400-600mgPOq8-12h;
max1800mg/d.
-Phenytoin(Dilantin),loadingdose15mg/kgat50mg/min,then100IVq8h.
ClassIc
-Flecainide(Tambocor)50-100mgPOq12h,max400mg/d.
-Propafenone(Rythmol)150-300mgPOq8h,max1200mg/d.
ClassIII
-Amiodarone(Cordarone)POloading400-1200mg/dindivideddosesx5-14
days,then200-400mgPOqdOR150mgslowIVover10min,then1
mg/minIVinfusionx6hoursthen0.5mg/minIVinfusionthereafter.
-Sotalol(Betapace)40-80mgPObid,max160mgbid.
Labs: SMA 12, Mg, calcium, CBC, cardiac enzymes, LFTs, ABG, drug
levels,thyroidfunctiontest.ECG,electrophysiologicstudy.
AcutePericarditis
Pericarditisisthemostcommondiseaseofthepericardium.Themostcommon
causeofpericarditisisviralinfection.This disorderischaracterizedbychest
pain, a pericardial friction rub, electrocardiographic changes, and pericardial
effusion.
I. Clinicalfeatures
A. Chest pain of acute infectious (viral) pericarditis typically develops in
youngeradults1to2weeksafteraviralillness.Thechestpainisof
suddenandsevereonset,withretrosternaland/orleftprecordialpainand
referraltothebackandtrapeziusridge.Painmaybeprecededbylow-
grade fever. Radiation to the arms may also occur. The pain is often
pleuritic(eg,accentuatedbyinspirationorcoughing)andmayalsobe
relievedbychangesinposture(uprightposture).
B. Apericardial frictionrubisthemostimportantphysicalsign.Itisoften
describedastriphasic,withsystolicandbothearly(passiveventricular
filling)andlate(atrialsystole)diastoliccomponents,ormorecommonly
abiphasic(systoleanddiastole).
C. Restingtachycardia(rarelyatrialfibrillation)andalow-gradefevermaybe
present.
CausesofPericarditis
Idiopathic
Infectious:Viral,bacterial,tubercu-
lous,parasitic,fungal
ConnectivetissuediseasesMeta-
bolic:uremia,hypothyroidismNeo-
plasm,radiation
Hypersensitivity:drug
Postmyocardialinjurysyndrome
Trauma
Dissectinganeurysm
Chylopericardium
II. Diagnostictesting
A. ECG changes. During the initial few days, diffuse (limb leads and
precordialleads)STsegmentelevationsarecommonintheabsenceof
reciprocal ST segment depression. PR segment depression is also
commonandreflectsatrialinvolvement.
B. Thechestradiographisoftenunrevealing,althoughasmallleftpleural
effusionmaybeseen.Anelevatederythrocytesedimentationrateand
C-reactive protein (CRP) and mild elevations of the white blood cell
countarealsocommon.
C. Labs: CBC, SMA 12, albumin, viral serologies: Coxsackie A & B,
measles,mumps,influenza,ASOtiter,hepatitissurfaceantigen,ANA,
rheumatoidfactor,anti-myocardialantibody,PPDwithcandida,mumps.
Cardiacenzymesq8hx4,ESR,bloodC&SX2.
D. Pericardiocentesis: Gram stain, C&S, cell count & differential,
cytology, glucose, protein, LDH, amylase, triglyceride, AFB, specific
gravity,pH.
48Pacemakers
E. Echocardiographyisthemostsensitivetestfordetectingpericardial
effusion,whichmayoccurwithpericarditis.
III. Treatmentofacutepericarditis(nonpurulent)
A. Ifeffusionpresentonechocardiography, pericardiocentesisshould be
performedandthecathetershouldbeleftinplacefordrainage.
B. Treatment of pain starts with nonsteroidal anti-inflammatory drugs,
meperidine, or morphine. In some instances, corticosteroids may be
requiredtosuppressinflammationandpain.
C. Anti-inflammatorytreatmentwithNSAIDsisfirst-linetherapy.
1. Indomethacin(Indocin)25mgtidor75mgSRqd,OR
2. Ketorolac(Toradol) 15-30mgIVq6h,OR
3. Ibuprofen(Motrin)600mgq8h.
D. Morphinesulfate5-15mgintramuscularlyevery4-6hours.Meperidine
(Demerol) may also be used, 50-100 mg IM/IV q4-6h prn pain and
promethazine(Phenergan)25-75mgIVq4h.
E. Prednisone,60mgdaily,tobereducedeveryfewdaysto40,20,10,
and5mgdaily.
F. Purulentpericarditis
1. Nafcillinoroxacillin2gmIVq4hANDEITHER
2. Gentamicinortobramycin100-120mgIV(1.5-2mg/kg);then80mg
(1.0-1.5mg/kg)IVq8h(adjustinrenalfailure)OR
3. Ceftizoxime (Cefizox)1-2gmIVq8h.
4. Vancomycin, 1 gm IV q12h, may be used in place of nafcillin or
oxacillin.
Pacemakers
Indicationsforimplantationofapermanentpacemakerarebasedonsymptoms,
the presence of heart disease and the presence of symptomatic
bradyarrhythmias.Pacemakersarecategorizedbyathree-tofive-lettercode
accordingtothesiteofthepacingelectrodeandthemodeofpacing.
I. Indicationsforpacemakers
A. First-degreeatrioventricular(AV)blockcanbeassociatedwithsevere
symptoms.PacingmaybenefitpatientswithaPRintervalgreaterthan
0.3seconds.TypeIsecond-degreeAVblockdoesnotusuallyrequire
permanentpacingbecauseprogressiontoahigherdegreeAVblockis
not common. Permanent pacing improves survival in patients with
completeheartblock.
B. PermanentpacingisnotneededinreversiblecausesofAVblock,such
aselectrolytedisturbancesorLymedisease.Implantationiseasierand
oflowercostwithsingle-chamberventriculardemand(VVI)pacemakers,
butuseofthesedevicesisbecominglesscommonwiththeadventof
dual-chamberdemand(DDD)pacemakers.
Pacemakers49
GenericPacemakerCodes
Position1
(chamber
paced)
Position2
(chamber
sensed)
Position3
(responseto
sensing)
Position4
(programma-
blefunctions;
ratemodula-
tion)
Position5
(antitachy-
arrhythmia
functions)
V--ventricle V--ventricle T--triggered P--program-
mablerate
and/oroutput
P--pacing
(antitachy-
arrhythmia)
A--atrium A--atrium I--inhibited M--multipro-
grammability
ofrate,output,
sensitivity,etc.
S--shock
D--dual(A
&V)
D--dual(A
&V)
D--dual(T&
I)
C--communi-
cating(telem-
etry)
D--dual(P+
S)
O--none O--none O--none R--ratemodu-
lation
O--none
O--none
C. Sicksinussyndrome(orsinusnodedysfunction)is themostcommon
reason for permanent pacing. Symptoms are related to the
bradyarrhythmiasofsicksinussyndrome.VVImodeistypicallyusedin
patientswithsicksinussyndrome,butrecentstudieshaveshownthat
DDDpacingimprovesmorbidity,mortalityandqualityoflife.
II. Temporarypacemakers
A. Temporarypacemakerleadsgenerallyareinsertedpercutaneously,then
positioned in the right ventricular apex and attached to an external
generator. Temporary pacing is used to stabilize patients awaiting
permanentpacemakerimplantation,tocorrectatransientsymptomatic
bradycardiaduetodrugtoxicityortosuppressTorsadesdePointesby
maintainingarateof85-100beatsperminuteuntilthecausehasbeen
eliminated.
B. Temporarypacingmayalsobeusedinaprophylacticfashioninpatients
atriskofsymptomaticbradycardiaduringasurgicalprocedureorhigh-
degreeAVblockinthesettingofanacutemyocardialinfarction.
C. Inemergentsituations,ventricularpacingcanbeinstitutedimmediately
bytranscutaneouspacingusingelectrodepadsappliedtothechestwall.
References
ACC/AHA Guidelines for Management of Patients with Acute Myocardial Infarction.
Circulation1999;100;1016-1030.
ACC/AHA Guidelines for Management of Patients with Unstable Angina and NonST-
SegmentElevationMyocardialInfarction.Circulation2000;102;1193-1209.
AcuteCoronarySyndromes(AcuteMyocardialInfarction).Circulation2000;102(suppI):
I172-I203.
50Pacemakers
Consensusrecommendationsforthemanagementofchronicheartfailure.AmJCard(supp)
Jan21,1999.
Bristow MR, et al: Heart failure management using implantable devices for ventricular
resynchronization:CompanionTrial.JofCardiacFailure,2000:6;276-284.
Yeghiazarians,Y.etal:UnstableAnginaPectoris:NEJM2000;342#2;101-112.
Wright,RSetal:UpdateonIntravenousFibrinolytic TherapyforAcuteMyocardialInfarction.
MayoClinProc2000;75:1185-92.
Adams,etal.HeartFailureSocietyGuidelines.Pharmacotherapy2000;20(5):496-520
Skrabal,etal.AdvancesintheTreatmentofCHF:NewApproachesforanOldDisease.
Pharmacotherapy2000;20(7):787-804.
OrotrachealIntubation51
Pulmonary Disorders
T.ScottGallacher,MD
RyanKlein,MD
MichaelKrutzik,MD
ThomasVovan,MD
OrotrachealIntubation
EndotrachealTubeSize(interiordiameter):
Women7.0-9.0mm
Men8.0-10.0mm
1. Preparesuctionapparatus.HaveAmbubagandmaskapparatussetupwith
100%oxygen;andensurethatpatientcanbeadequatelybagventilatedand
suctionapparatusisavailable.
2. Ifsedationand/orparalysisis required,considerrapidsequenceinductionas
follows:
A. Fentanyl(Sublimaze)50mcgincrementsIV(1mcg/kg)with:
B. Midazolam(Versed)1mgIVq2-3min.max0.1-0.15mg/kgfollowedby:
C. Succinylcholine (Anectine) 0.6-1.0 mg/kg, at appropriate intervals; or
vecuronium(Norcuron)0.1mg/kgIVx1.
D. Propofol(Diprivan):0.5mg/kgIVbolus.
E. Etomidate(Amidate):0.3-0.4mg/kgIV.
3. Positionthepatient'sheadinthesniffingpositionwithheadflexedatneck
andextended.Ifnecessary,elevatetheheadwithasmallpillow.
4. Ventilate the patient with bag mask apparatus and hyperoxygenate with
100%oxygen.
5. Hold laryngoscope handle with left hand, and use right hand to open the
patients mouth. Insert blade along the right side of mouth to the base of
tongue,andpushthetonguetotheleft.Ifusingcurvedblade,advanceitto
thevallecula(superiortoepiglottis),andliftanteriorly,beingcarefulnotto
exert pressure on the teeth. If using a straight blade, place beneath the
epiglottisandliftanteriorly.
6. Placeendotrachealtube(ETT)intorightcornerofmouthandpassitthrough
the vocal cords; stop just after the cuff disappears behind vocal cords. If
unsuccessfulafter30seconds,stopandresumebagandmaskventilation
beforere-attempting.AstilettetomaintaintheshapeoftheETTinahockey
stickshapemaybeused.Removestiletteafterintubation.
7. Inflatecuffwithsyringekeepingcuffpressure<20cmH
2
O,andattachthe
tubetoanAmbubagorventilator.Confirmbilateral,equalexpansionofthe
chestandequalbilateralbreathsounds.Auscultatetheabdomentoconfirm
thattheETTisnotintheesophagus.Ifthereisanyquestionaboutproper
ETT location, repeat laryngoscopy with tube in place to be sure it is
endotracheal. Remove the tube immediately if there is any doubt about
properlocation.Securethetubewithtapeandnotecentimetermarkatthe
mouth.Suctiontheoropharynxandtrachea.
8. Confirm proper tube placement with a chest x-ray (tip of ETT should be
between the carina and thoracic inlet, or level with the top of the aortic
notch).
52NasotrachealIntubation
NasotrachealIntubation
Nasotracheal intubation is the preferred method of intubation if prolonged
intubationisanticipated(increasedpatientcomfort).Intubationwillbefacilitated
if the patient is awake and spontaneously breathing. There is an increased
incidenceofsinusitiswithnasotrachealintubation.
1. Spray the nasal passage with a vasoconstrictor such as cocaine 4% or
phenylephrine 0.25% (Neo-Synephrine). If sedation is required before
nasotrachealintubation,administermidazolam(Versed)0.05-0.1mg/kgIV
push.Lubricatethenasalairwaywithlidocaineointment.
TubeSize:
Women7.0mmtube
Men8.0,9.0mmtube
2. Place the nasotracheal tube into the nasal passage, and guide it into
nasopharynxalongaU-shapedpath.Monitorbreathsoundsbylisteningand
feelingtheendoftube.Asthetubeenterstheoropharynx, gradually guidethe
tubedownward.Ifthe breathsoundsstop,withdrawthetube1-2cmuntil
breathsoundsareheardagain.Repositionthetube,and,ifnecessary,extend
the head and advance. If difficulty is encountered, perform direct
laryngoscopyandinserttubeunderdirectvisualization.
3. Successful intubation occurs when the tube passes through the cords; a
coughmayoccurandbreathsoundswillreachmaximumintensityifthetube
iscorrectlypositioned.Confirmcorrectplacementbycheckingforbilateral
breathsoundsandexpansionofthechest.
4.Confirmpropertubeplacementwithchestx-ray.
RespiratoryFailureandVentilatorManagement
I. Indicationsforventilatorysupport.Respirations>35,vitalcapacity<15
mL/kg,negativeinspiratoryforce<-25,pO
2
<60on50%0
2
.pH<7.2,pCO
2
>55,severe,progressive,symptomatichypercapniaand/orhypoxia,severe
metabolicacidosis.
II. Initiationofventilatorsupport
A. Noninvasive positive pressure ventilation may be safely utilized in
acute hypercapnic respiratory failure, avoiding the need for invasive
ventilation and accompanying complications. It is not useful in
normocapnicorhypoxemicrespiratoryfailure.
B. Intubation
1. Preparesuctionapparatus,laryngoscope,endotrachealtube(No.
8); clear airway and place oral airway, hyperventilate with bag and
maskattachedtohigh-flowoxygen.
2. Midazolam(Versed)1-2mgIVbolusesuntilsedated.
3. Intubate,inflatecuff,ventilatewithbag,auscultatechest,andsuction
trachea.
C.Initialorders
1. Assistcontrol(AC)8-14breaths/min,tidalvolume=750mL(6cc/kg
idealbodyweight),FiO
2
=100%,PEEP=3-5cmH
2
O,Setratesothat
minuteventilation(VE)isapproximately10L/min.Alternatively,use
intermittentmandatoryventilation(IMV)modewithsametidalvolume
VentilatorManagement53
andratetoachievenear-totalventilatorysupport.Pressuresupportat
5-15cmH
2
OinadditiontoIMVmaybeadded.
2. ABGshouldbeobtained.CheckABGforadequateventilationand
oxygenation. If PO
2
is adequate and pulse oximetry is >98%, then
titrateFiO
2
toasafelevel(FIO
2
<60%)byobservingthesaturationvia
pulseoximetry.RepeatABGwhentargetFiO
2
isreached.
3. Chest x-ray for tube placement, measure cuff pressure q8h
(maintain<20mmHg),pulseoximeter,arterialline,and/ormonitor
endtidalCO
2
.Maintainoxygensaturation>90-95%.
VentilatorManagement
A. Decreasedminuteventilation.Evaluatepatientandruleoutcomplica-
tions (endotracheal tube malposition, cuff leak, excessive secretions,
bronchospasms,pneumothorax,worseningpulmonarydisease,sedative
drugs,pulmonary infection).Readjustventilatorratetomaintainmechani-
cally assisted minute ventilation of 10 L/min. If peak airway pressure
(AWP)is>45cmH
2
O,decreasetidalvolumeto7-8L/kg(withincrease
inrateifnecessary),ordecreaseventilatorflowrate.
B. Arterialsaturation>94%andpO
2
>100,reduceFIO
2
(each1%decrease
inFIO
2
reducespO
2
by7mmHg);onceFIO
2
is<60%,PEEPmaybe
reducedbyincrementsof2cmH
2
OuntilPEEPis3-5cmH
2
O.MaintainO
2
saturationof>90%(pO
2
>60).
C. Arterialsaturation<90%andpO
2
<60,increaseFIO
2
upto60-100%,
thenconsiderincreasingPEEPbyincrementsof3-5cmH
2
O(PEEP>10
requires a PA catheter). Add additional PEEP until oxygenation is
adequatewithanFIO
2
of<60%.
D. Excessively low pH, (pH <7.33 because of respiratory acido-
sis/hypercapnia): Increase rate and/or tidal volume. Keep peak airway
pressure<40-50cmH
2
Oifpossible.
E. Excessively high pH (>7.48 because of respiratory alkalosis/hypo-
capnia):Reducerateand/ortidalvolume.Ifthepatientis breathingrapidly
aboveventilatorrate,considersedation.
F. Patient fighting ventilator: Consider IMV or SIMV mode, or add
sedationwithorwithoutparalysis.Paralyticagentsshouldnotbeused
withoutconcurrentamnesiaand/orsedation.
G. Sedation
1. Midazolam(Versed)0.05mg/kgIVPx1,then0.02-0.1mg/kg/hrIV
infusion.Titrateinincrementsof25-50%.
2. Lorazepam(Ativan)1-2mgIVql-2hpmsedationor0.05mg/kgIVP
x1,then0.025-0.2mg/kg/hrIVinfusion.Titrateinincrementsof25-
50%.
3. Morphinesulfate2-5mgIVq1hor0.03-0.05mg/kg/hIVinfusion(100
mgin250mLD5W)titrated.
4. Propofol (Diprivan): 50 mcg/kg bolus over 5 min, then 5-50
mcg/kg/min.Titrateinincrementsof5mcg/kg/min.
H. Paralysis(withsimultaneousamnesia)
1. Vecuronium(Norcuron)0.1mg/kgIV,then0.06mg/kg/hIVinfusion;
intermediateacting,maximumneuromuscularblockadewithin3-5min.
Half-life60min,OR
54InverseRatioVentilation
2. Cisatracurium (Nimbex) 0.15 mg/kg IV, then 0.3 mcg/kg/min IV
infusion,titratebetween0.5-10mcg/kg/min.Intermediateactingwith
half-lifeof25minutes.Drugofchoiceforpatientswithrenalorliver
impairment,OR
3. Pancuronium(Pavulon)0.08mg/kgIV,then0.03mg/kg/hinfusion.
Long acting, half-life 110 minutes; may cause tachycardia and/or
hypertension,OR
4. Atracurium(Tracrium)0.5mg/kgIV,then0.3-0.6mg/kg/hinfusion,
shortacting;half-life20minutes.Histaminereleasingpropertiesmay
causebronchospasmand/orhypotension.
5. Monitor level of paralysis with a peripheral nerve stimulator. Adjust
neuromuscularblockerdosagetoachieveatrain-of-four(TOF)of90-
95%;ifinverseratioventilationisbeingused,maintainTOFat100%.
I. Lossattidalvolume:If adifferencebetweenthetidalvolumesettingand
the delivered volume occurs, check for a leak in the ventilator or
inspiratoryline.Checkforapoorsealbetweentheendotrachealtubecuff
ormalpositionofthecuffinthesubglotticarea.Ifachesttubeispresent,
checkforairleak.
J. High peak pressure: If peak pressure is >40-50, consider
bronchospasm,secretion,pneumothorax,ARDS,agitation.Suctionthe
patientandauscultatelungs.Obtainchestradiographifpneumothorax,
pneumoniaorARDSissuspected.Checkplateaupressuretodifferenti-
ateairwayresistancefromcompliancecauses.
InverseRatioVentilation
1. Indications: ARDS physiology, pAO
2
<60 mm Hg, FIO
2
>0.6, peak airway
pressure>45cmH
2
0,orPEEP>15cmH
2
0.Thistypeofventilatorysupport
requiresheavysedationandrespiratorymusclerelaxation.
2. Setoxygenconcentration(FIO
2
)at1.0;inspiratorypressureattoaofthe
peakairwaypressureonstandardventilation.Settheinspiration:expiration
ratioat1:1;setrateat<15breaths/min.Maintaintidalvolumebyadjusting
inspiratorypressures.
3. MonitorPaO
2
,oxygensaturation(bypulseoximetry),PaCO
2
,endtidalPCO
2
,
PEEP,meanairwaypressure,heartrate,bloodpressure,SVO
2
,andcardiac
output.
4. ItSaO
2
remains<0.9,considerincreasingI:Eratio(2:1,3:1),butattemptto
keep I:E ratio <2:1. If SaO
2
remains <0.9, increase PEEP or return to
conventionalmode.Ifhypotensiondevelops,ruleouttensionpneumothorax,
administer intravascular volume or pressor agents, decrease I:E ratio, or
returntoconventionalventilationmode.
VentilatorWeaning
I. Ventilatorweaningparameters
A. Patientalertandrested
B. PaO
2
>70mmHgonFiO
2
<50%
C. PaCO
2
<50mmHg;pH>7.25
D. NegativeInspiratoryForce(NIF)lessthan-40cmH
2
O
VentilatorWeaning55
E. VitalCapacity>10-15mL/kg(800-1000mL)
F. MinuteVentilation(VE)<10L/min;respirations<24breathspermin
G. Maximalvoluntaryminute(MVV)ventilationdoublesthatofrestingminute
ventilation(VE).
H. PEEP<5cmH
2
O
I. Tidalvolume5-8mL/kg
J. Respiratoryratetotidalvolumeratio<105
K. Nochestwallorcardiovascularinstabilityorexcessivesecretions
II. Weaningprotocols
A. Weaning is considered when patient medical condition (ie, cardiac,
pulmonary)statushasstabilized.
B. Indicationsforterminationofweaningtrial
1. PaO
2
fallsbelow55mmHg
2. Acutehypercapnia
3. Deteriorationofvitalsignsorclinicalstatus(arrhythmia)
C. Rapid T-tube weaning method for short-term (<7 days) ventilator
patientswithoutCOPD
1. Obtainbaselinerespiratoryrate,pulse,bloodpressureandarterial
bloodgasesoroximetry.Discontinuesedation,havethewell-rested
patient sit in bed or chair. Provide bronchodilators and suctioning if
needed.
2. AttachendotrachealtubetoaT-tubewithFiO
2
>10%greaterthan
previouslevel.SetT-tubeflow-byratetoexceedpeakinspiratoryflow.
3. PatientswhoaretriedonT-tubetrialshouldbeobservedcloselyfor
signs of deterioration. After initial 15-minute interval of spontaneous
ventilation,resumemechanicalventilationandcheckoxygensaturation
ordrawanarterialbloodgassample.
4. Ifthe30-minutebloodgasisacceptable,a60-minuteintervalmay
be attempted. After each interval, the patient is placed back on the
ventilatorforanequalamountoftime.
5. Ifthe60-minuteintervalbloodgasisacceptableandthepatientis
withoutdyspnea,andifbloodgasesareacceptable,extubationmaybe
considered.
D. Pressuresupportventilationweaningmethod
1. Pressuresupportventilationisinitiatedat5-25cmH
2
O.Setlevel
tomaintainthespontaneoustidalvolumeat7-15mL/kg.
2. Gradually decrease the level of pressure support ventilation in
increments of 3-5 cm H
2
O according to the ability of the patient to
maintainsatisfactoryminuteventilation.
3. Extubationcanbeconsideredatapressuresupportventilationlevel
of5cmH
2
Oprovidedthatthepatientcanmaintainstablerespiratory
statusandbloodgasses.
E. Intermittentmandatoryventilation(IMV)weaningmethod
1. Obtainbaselinevitalsignsanddrawbaselinearterialbloodgases
or pulse oximetry. Discontinue sedation; consider adding pressure
supportof10-15cmH
2
O.
2. ChangetheventilatorfromassistcontroltoIMVmode;orifalready
onIMVmode,decreasetherateasfollows:
a. Patientswithnounderlyinglungdiseaseandonventilatorfora
briefperiod(<1week).
56PulmonaryEmbolism
(1) DecreaseIMVrateat30minintervalsby1-3breathperminat
each step, starting at rate of 8-10 until a rate for zero is
reached.
(2) IfeachstepistoleratedandABGisadequate(pH>7.3-7.35),
extubationmaybeconsidered.
(3) Alternatively:Thepatientmaybewatchedonminimalsupport
(ie, pressure support with CPAP) after IMV rate of zero is
reached. If no deterioration is noted, extubation may be
accomplished.
b. PatientswithCOPDorprolongedventilatorsupport(>1week)
(1) Begin with IMV at frequency of 8 breath/minute, with tidal
volumeof10mL/kg,withanFiO
2
10%greaterthanprevious
setting.Checkend-tidalCO
2
.
(2) ABGshouldbedrawnat30-and60-minuteintervalstocheck
foradequateventilationandoxygenation.Ifthepatientand/or
blood gas deteriorate during weaning trial, then return to
previousstablesetting.
(3) DecreaseIMVrateinincrementsof1-2breathperhourifthe
patientisclinicalstatusandbloodgasesremainstable.Check
ABGandsaturationone-halfhourafteranewrateisset.
(4) If the patient tolerates an IMV rate of zero, decrease the
pressuretosupportinincrementsof2-5cmH
2
Operhouruntil
apressuresupportof5cmH
2
Oisreached.
(5) Observe the patient for an additional 24 hours on minimal
supportbeforeextubation.
3. Causes of inability to wean patients from ventilators:
Bronchospasm, active pulmonary infection, secretions, small
endotrachealtube,weaknessofrespiratorymuscle,lowcardiacoutput.
PulmonaryEmbolism
Approximately 300,000 Americans suffer pulmonary embolism each year.
Amongthoseinwhomtheconditionisdiagnosed,2percentdiewithinthefirst
dayand10percenthaverecurrentpulmonaryembolism.
I. Diagnosisofpulmonaryembolism
A. Pulmonary embolism should be suspected in any patient with new
cardiopulmonary symptoms orsignsandsignificantriskfactors.Ifnoother
satisfactoryexplanationcanbefoundinapatientwithfindingssuggestive
ofpulmonaryembolism,theworkupforPEmustbepursuedtocomple-
tion.
B. Signs and symptoms of pulmonary embolism. Pleuritic chest pain,
unexplainedshortnessofbreath,tachycardia,hypoxemia,hypotension,
hemoptysis,cough,syncope.Theclassictriadofdyspnea,chestpain,and
hemoptysisisseeninonly20%ofpatients.Themajorityofpatientshave
onlyafewsubtlesymptomsorareasymptomatic.
C. Massivepulmonaryembolimaycausethesuddenonsetofprecordialpain,
dyspnea,syncope,orshock.Otherfindingsincludedistendedneckveins,
cyanosis,diaphoresis,pre-cordialheave,aloudpulmonicvalvecompo-
nent of the second heart sound. Right ventricular S3, and a tricuspid
insufficiency.
VentilatorWeaning57
D. Deep venous thrombosis may manifest as an edematous limb with an
erythrocyanoticappearance,dilatedsuperficialveins,andelevatedskin
temperature.
FrequencyofSymptomsandSignsinPulmonaryEmbolism
Symptoms Frequency
(%)
Signs Frequency
(%)
Dyspnea
Pleuriticchestpain
Apprehension
Cough
Hemoptysis
Sweating
Non-pleuriticchestpain
84
74
59
53
30
27
14
Tachypnea(>16/min)
Rales
AccentuatedS2
Tachycardia
Fever(>37.8C)
Diaphoresis
S3orS4gallop
Thrombophlebitis
92
58
53
44
43
36
34
32
II. Riskfactorsforpulmonaryembolism
A.Venousstasis.Prolongedimmobilization,hipsurgery,stroke,myocardial
infarction,heartfailure,obesity,varicoseveins,anesthesia,age>65years
old.
B.Endothelial injury. Surgery, trauma, central venous access catheters,
pacemakerwires,previousthromboembolicevent.
C.Hypercoagulable state. Malignant disease, high estrogen level (oral
contraceptives).
D.Hematologic disorders. Polycythemia, leukocytosis, thrombocytosis,
antithrombin III deficiency, protein C deficiency, protein S deficiency,
antiphospholipidsyndrome,inflammatoryboweldisease,factor5Leiden
defect.
III. Diagnosticevaluation
A. Chest radiographs are nonspecific and insensitive, and findings are
normal in up to 40 percent of patients with pulmonary embolism.
Abnormalitiesmayincludeanelevatedhemidiaphragm,focalinfiltrates,
atelectasis,andsmallpleuraleffusions.
B. Electrocardiographyisnonspecific andoftennormal.Themostcommon
abnormalityissinustachycardia.OtherfindingsmayincludeST-segment
orT-wavechanges.Occasionally,acuterightventricularstraincausestall
peakedPwavesinleadII,rightaxisdeviation,rightbundlebranchblock,
oratrialfibrillation.
C. Bloodgasstudies.Thereisnolevelofarterialoxygenthatcanruleout
pulmonary embolism. Most patients with pulmonary embolism have a
normalarterialoxygen.
D. Ventilation-perfusionscan
1. Patientswithaclearlynormalperfusionscandonothaveapulmonary
embolism,andlessthan5percentofpatientswithnear-normalscan
haveapulmonaryembolism.Ahigh-probabilityscanhasa90percent
probabilityofapulmonaryembolism.
2. Alow-probabilityV/Qscancanexcludethediagnosisofpulmonary
embolismonlyifthepatienthasaclinicallylowprobabilityofpulmo-
naryembolism.
58PulmonaryEmbolism
3. IntermediateV/Qscansarenotdiagnosticandusuallyindicatethe
need for further diagnostic testing. One-third of patients with inter-
mediatescanshaveapulmonaryembolismandshouldhaveafollow-
upchestCTorpulmonaryangiography.
E. Venousimaging
1. IftheV/Qscanisnondiagnostic,aworkupfordeepvenousthrombo-
sis(DVT)shouldbepursuedusingduplexultrasound.Theidentifica-
tionofDVTinapatientwithsignsandsymptomssuggestingpulmo-
naryembolismprovesthediagnosisofpulmonaryembolism.Adeep
venous thrombosis can be found in 80% of cases of pulmonary
emboli.
2. InabilitytodemonstratetheexistenceofaDVTdoesnotsignificantly
lower the likelihood of pulmonary embolism because clinically
asymptomaticDVTmaynotbedetectable.
3. PatientswithanondiagnosticV/Qscanandnodemonstrablesiteof
DVTshouldproceedtochestCTorpulmonaryangiography.
F. ChestCTmaybe usedinplaceofpulmonaryangiographyinpatients
with abnormal chest x-ray in whom V/Q scan is nondiagnostic, or in
presenceofanintermediateprobabilityofPEonV/Qscan.ChestCTis
associated with fewer complications than pulmonary angiography.
However,chestCToffersamorelimitedviewofthispulmonaryfieldand
doesnotallowformeasurementofpulmonaryarterypressure.
G. Angiography.Contrastpulmonaryarteriographyisthegoldstandardfor
thediagnosisofpulmonaryembolism.False-negativeresultsoccurin2-
10%ofpatients.Angiographycarriesalowriskofcomplications(minor
5%,majornonfatal1%,fatal0.5%).
IV. Managementofacutepulmonaryembolisminstablepatients
A. Oxygenshouldbeinitiatedforallpatients.
B. Antithrombotictherapy
1. Heparin therapy should be started as soon as the diagnosis of
pulmonary embolism is suspected. Full-dose heparin can be given
immediatelyaftermajorsurgery.
2. Unfractionated heparin is administrated as 80 U/kg IVP, then 18
U/kg/h IV infusion. Obtain an aPTT in 6 hours, and adjust dosage
based on the table below to maintain the aPTT between 60-85
seconds.Contraindicationstoheparinincludeactiveinternalbleeding
andrecentandsignificanttrauma.
HeparinMaintenanceDoseAdjustment
aPTTs Bolus
Dose
Stopinfu-
sion
RateChange,
mL/h*
RepeataPTT
<50 5000U 0min +3(increaseby
150U/h)
6h
50-59 0 0min +2 (increaseby
100U/h)
6h
60-85 0 0min 0(nochange) nextAM
PulmonaryEmbolism59
aPTTs Bolus
Dose
Stopinfu-
sion
RateChange,
mL/h*
RepeataPTT
86-95 0 0min -1(decreaseby
50U/h)
nextAM
96-120 0 30min -2(decreaseby
100U/h)
6h
>120 0 60min -3(decreaseby
150U/h)
6h
*50U/mL
3. Platelet count should be monitored during heparin therapy;
thrombocytopeniadevelopsin5%ofpatientsafter3-7daysoftherapy.
Heparinmayrarelyinducehyperkalemia,whichresolvesspontaneously
upondiscontinuation.
4. Low-molecular-weight heparin (LMWH) is as effective as
unfractionated heparin for uncomplicated PE. It does not require
monitoring and may allow for earlier hospital discharge. Enoxaparin
(Lovenox)canbeusedforDVTwithuncomplicatedPE:1mg/kgSC
q12hx5day minimum. Therapy withLMWHshouldoverlapwarfarinfor
3-4days.
5. Warfarin (Coumadin) may be started as soon as the diagnosis of
pulmonary embolism is confirmed and heparin has been initiated.
Startingdoseis10mgPOqdfor3days.Thedoseisthenadjustedto
keeptheInternationalNormalizedRatio(INR)at2.0-3.0.Thetypical
dosage is 2.0-7.5 mg PO qd. Heparin and warfarin regimens are
overlapped for 3 to 5 days until the INR is 2.0-3.0, then heparin is
discontinued.
6. Therapywithwarfarinisgenerallycontinuedfor3-6months.Inpatients
withanongoingriskfactororfollowingasecondepisodeofDVT,life-
longanticoagulationwithwarfarinmaybenecessary.
C.Thrombolysis
1. Unstable patients (systolic <90 mm Hg) with proven pulmonary
embolismrequireimmediateclotlysisbythrombolytictherapy.Tissue
plasminogen activator (Activase) is recommended because it is the
fastest-actingthrombolyticagent.
2. Contraindicationstothrombolytics
a. Absolutecontraindications.Activebleeding,cerebrovascularacci-
dentorsurgerywithinthepast2months,intracranialneoplasms.
b. Relative contraindications. Recent gastrointestinal bleeding,
uncontrolledhypertension,recenttrauma(cardiopulmonaryresusci-
tation),pregnancy.
3. Alteplase(tPA,Activase).100mgbyperipheralIVinfusionover2hr.
Heparintherapyshouldbeinitiatedaftercessationofthethrombolytic
infusion.Heparinisstartedwithoutaloadingdoseat18U/kg/hrwhen
theaPTTis1.5timescontrolrate.
D.Fluidandpharmacologicmanagement.Inacutecorpulmonale,gentle
pharmacologicpreloadreductionwithfurosemideunloadsthecongested
pulmonary circuit and reduces right ventricular pressures. Hydralazine,
60Asthma
isoproterenol, or norepinephrine may be required. Pulmonary artery
pressuremonitoringmaybehelpful.
E.Emergency thoracotomy. Emergency surgical removal of embolized
thrombusisreservedforinstanceswhenthereisanabsolutecontraindica-
tiontothrombolysisorwhenthepatient'sconditionhasfailedtoimprove
after thrombolysis. Cardiac arrest from pulmonary embolism is an
indicationforimmediatethoracotomy.
Asthma
Asthmaisthemostcommonchronicdiseaseamongchildren.Asthmatriggers
includeviralinfections;environmentalpollutants,suchastobaccosmoke;as-
pirin,nonsteroidalanti-inflammatorydrugs,andsustainedexercise,particularly
incoldenvironments.
I. Diagnosis
A. Symptoms of asthma may include episodic complaints of breathing
difficulties,seasonalornighttimecough,prolongedshortnessofbreath
afterarespiratoryinfection,ordifficultysustainingexercise.
B.Wheezingdoesnotalwaysrepresentasthma.Wheezingmaypersistfor
weeksafteranacutebronchitisepisode.Patientswithchronicobstructive
pulmonarydiseasemayhaveareversiblecomponentsuperimposedon
theirfixedobstruction.Etiologiccluesincludeapersonalhistoryofallergic
disease,suchasrhinitisoratopicdermatitis,andafamilyhistoryofallergic
disease.
C.Thefrequencyofdaytimeandnighttimesymptoms,durationofexacerba-
tionsandasthmatriggersshouldbeassessed.
D.Physical examination. Hyperventilation, use of accessory muscles of
respiration, audible wheezing, and a prolonged expiratory phase are
common.Increasednasalsecretionsorcongestion,polyps,andeczema
maybepresent.
E. Measurement of lung function. An increase in the forced expiratory
volumeinonesecond(FEV
1
)of12%aftertreatmentwithaninhaledbeta
2
agonistissufficienttomakethediagnosisofasthma.A12%changein
peakexpiratoryflowrate(PEFR)measuredonapeak-flowmeterisalso
diagnostic.
II. Treatmentofasthma
A. Beta
2
agonists
1. Inhaledshort-actingbeta
2
-adrenergicagonistsarethemosteffective
drugsavailablefortreatmentofacutebronchospasmandforpreven-
tionofexercise-inducedasthma.Levalbuterol,theR-isomerofracemic
albuterol,offersnosignificantadvantageoverracemicalbuterol.
2. Salmeterol,along-actingbeta
2
agonist,hasarelativelyslowonsetof
actionandaprolongedeffect.Salmeterolshouldnotbeusedinthe
treatmentofacutebronchospasm.Patientstakingsalmeterolshould
useashort-actingbeta
2
agonistasneededtocontrolacutesymptoms.
Twice-dailyinhalationofsalmeterolhasbeeneffectiveformaintenance
treatmentincombinationwithinhaledcorticosteroids.
3. Adverseeffectsofbeta
2
agonists.Tachycardia,palpitations,tremor
and paradoxical bronchospasm can occur. High doses can cause
hypokalemia.
Asthma61
DrugsforAsthma
Drug Formulation Dosage
Inhaledbeta
2
-adrenergicagonists,short-acting
Albuterol
Proventil
Proventil-HFA
Ventolin
Ventolin Rotacaps
metered-doseinhaler(90
:g/puff)
dry-powderinhaler(200
:g/inhalation)
2puffsq4-6hPRN
1-2capsulesq4-6hPRN
Albuterol
Proventil
multi-dosevials
Ventolin Nebules
Ventolin
nebulized 2.5mgq4-6hPRN
Levalbuterol- Xopenex nebulized 0.63-1.25mgq6-8hPRN
Inhaledbeta2-adrenergicagonist,long-acting
Salmeterol
Serevent
Serevent Diskus
metered-doseinhaler(21
:g/puff)
dry-powderinhaler(50
:g/inhalation)
2puffsq12h
1inhalationq12h
InhaledCorticosteroids
Beclomethasone
dipropionate
Beclovent
Vanceril
VancerilDouble-Strength
metered-doseinhaler(42
:g/puff)
(84:g/puff)
4-8puffsbid
2-4puffsbid
Budesonide
Pulmicort Turbuhaler
dry-powderinhaler(200
:g/inhalation)
1-2inhalationsbid
Flunisolide- AeroBid metered-doseinhaler
(250:g/puff)
2-4puffsbid
FluticasoneFlovent
Flovent Rotadisk
metered-doseinhaler
(44,110or220:g/puff)
dry-powderinhaler(50,
100or250:g/inhalation)
2-4puffsbid
(44:g/puff)
1inhalationbid
(100:g/inhalation)
Triamcinoloneacetonide
Azmacort
metered-doseinhaler
(100:g/puff)
2puffstid-qidor4puffs
bid
LeukotrieneModifiers
62Asthma
Drug Formulation Dosage
Montelukast- Singulair tablets 10mgqhs
Zafirlukast- Accolate tablets 20mgbid
Zileuton- Zyflo tablets 600mgqid
MastCellStabilizers
Cromolyn
Intal
metered-doseinhaler
(800:g/puff)
2-4puffstid-qid
Nedocromil
Tilade
metered-doseinhaler
(1.75mg/puff)
2-4puffsbid-qid
PhosphodiesteraseInhibitor
Theophylline
Slo-Bid Gyrocaps,Theo-
Dur,Unidur
extended-releasecap-
sulesortablets
100-300mgbid
B.Inhaledcorticosteroids
1. Regularuseofaninhaledcorticosteroidcansuppressinflammation,
decrease bronchial hyperresponsiveness and decrease symptoms.
Inhaled corticosteroids are recommended for treatment of patients
withmildormoderatepersistentasthmaaswellasthosewithsevere
disease.
2. Adverseeffects.Inhaledcorticosteroidsareusuallyfreeoftoxicity.
Dose-dependentslowingoflineargrowthmayoccurwithin6-12weeks
in some children. Decreased bone density, glaucoma and cataract
formation have been reported. Churg-Strauss vasculitis has been
reportedrarely.Dysphoniaandoralcandidiasiscanoccur.Theuseof
aspacerdeviceandrinsingthemouthafterinhalationdecreasesthe
incidenceofcandidiasis.
C.Leukotrienemodifiers
1. Leukotrienesincreaseproductionofmucusandedemaoftheairway
wall,andmaycausebronchoconstriction.Montelukastandzafirlukast
are leukotriene receptor antagonists. Zileuton inhibits synthesis of
leukotrienes.
2. Montelukast (Singulair) is modestly effective for maintenance
treatmentofintermittentorpersistentasthma.Itistakenoncedailyin
the evening. It is less effective than inhaled corticosteroids, but
addition of montelukast may permit a reduction in corticosteroid
dosage. Montelukast added to oral or inhaled corticosteroids can
improvesymptoms.
3. Zafirlukast (Accolate) is modestly effective for maintenance
treatmentofmild-to-moderateasthmaItislesseffectivethaninhaled
corticosteroids.Takingzafirlukastwithfoodmarkedlydecreasesits
bioavailability. Theophylline can decrease its effect. Zafirlukast
increasesserumconcentrationsof oral anticoagulantsandmaycause
bleeding.Infrequentadverseeffectsincludemildheadache,gastroin-
Asthma63
testinaldisturbancesandincreasedserumaminotransferaseactivity.
Drug-inducedlupusandChurg-Straussvasculitishavebeenreported.
4. Zileuton(Zyflo)ismodestlyeffectiveformaintenancetreatment,but
itistakenfourtimesadayandpatientsmustbemonitoredforhepatic
toxicity.
D.Cromolyn(Intal)andnedocromil(Tilade)
1. Cromolyn sodium, an inhibitor of mast cell degranulation, can
decreaseairwayhyperresponsivenessinsomepatientswithasthma.
The drug has no bronchodilating activity and is useful only for
prophylaxis.Cromolynhasvirtuallynosystemictoxicity.
2. Nedocromil has similar effects as cromolyn. Both cromolyn and
nedocromilaremuchlesseffectivethaninhaledcorticosteroids.
E.Theophylline
1. Oral theophylline has a slower onset of action than inhaled beta
2
agonistsandhaslimitedusefulnessfortreatmentofacutesymptoms.
It can, however, reduce the frequency and severity of symptoms,
especially in nocturnal asthma, and can decrease inhaled
corticosteroidrequirements.
2. Whentheophyllineisusedalone,serumconcentrationsbetween8-12
mcg/mLprovideamodestimprovementisFEV
1
.Serumlevelsof15-
20mcg/mLareonlyminimallymoreeffectiveandareassociatedwith
ahigherincidenceofcardiovascularadverseevents.
F. Oral corticosteroids are the most effective drugs available for acute
exacerbationsofasthmaunresponsivetobronchodilators.
1. Oral corticosteroids decrease symptoms and may prevent an early
relapse. Chronic use of oral corticosteroids can cause glucose
intolerance, weight gain, increased blood pressure, osteoporosis,
cataracts, immunosuppression and decreased growth in children.
Alternate-day use of corticosteroids can decrease the incidence of
adverseeffects,butnotofosteoporosis.
2. Prednisone,prednisoloneormethylprednisolone(Solu-Medrol),
40-60mgqd;forchildren,1-2mg/kg/daytoamaximumof60mg/day.
Therapyiscontinuedfor3-10days.Theoralsteroiddosagedoesnot
needtobetaperedaftershort-coursebursttherapyifthepatientis
receivinginhaledsteroidtherapy.
G. Choiceofdrugs
1. Patientswithinfrequentmildsymptomsofasthmamayrequireonly
intermittentuse,asneeded,ofashort-actinginhaledbeta
2
-adrenergic
agonist.Overuseofinhaledshort-actingbeta
2
agonistsormorethan
twiceaweekindicatesthataninhaledcorticosteroidshouldbeadded
tothetreatmentregimen.
PharmacotherapyforAsthmaBasedonDiseaseClassification
Classification Long-termcontrolmedications Quick-reliefmedications
Mildintermit-
tent
Short-actingbeta
2
agonistas
needed
Mildpersistent Low-doseinhaledcorticosteroid
orcromolynsodium(Intal)or
nedocromil(Tilade)
Short-actingbeta
2
agonistas
needed
64ChronicObstructivePulmonaryDisease
Classification Long-termcontrolmedications Quick-reliefmedications
Moderateper-
sistent
Medium-doseinhaledcortico-
steroidplusalong-acting
bronchodilator(long-actingbeta
2
agonist)
Short-actingbeta
2
agonistas
needed
Severepersis-
tent
High-doseinhaledcorticosteroid
plusalong-actingbronchodilator
andsystemiccorticosteroid
Short-actingbeta
2
agonistas
needed
III.Managementofacuteexacerbations
A.High-dose, short-acting beta
2
agonists delivered by a metered-dose
inhalerwithavolumespacerorviaanebulizerremainsthemainstayof
urgenttreatment.
B.Most patients require therapy with systemic corticosteroids to resolve
symptomsandpreventrelapse.
C.HospitalizationshouldbeconsideredifthePEFRremainslessthan70%
ofpredicted.PatientswithaPEFRlessthan50%ofpredictedwhoexhibit
anincreasingpCO
2
levelanddecliningmentalstatusarecandidatesfor
intubation.
D.Non-invasiveventilationwithbilevelpositiveairwaypressure(BIPAP) may
beusedtorelievethework-of-breathingwhileawaitingtheeffectsofacute
treatment, provided that consciousness and the ability to protect the
airwayhavenotbeencompromised.
ChronicObstructivePulmonaryDisease
Chronicobstructivepulmonarydiseaseaffectsmorethan20millionAmericans.
This condition is composed of three distinct entities: 1) chronic bronchitis; 2)
emphysema; and 3) peripheral airway disease. The greatest percentage of
patientswithCOPDhavechronicbronchitis.
I. Clinicalevaluation
A. ThemajorityofpatientswithCOPDwillhaveeitherahistoryofcigarette
smoking or exposure to second-hand cigarette smoke. Occasionally,
patients will develop COPD from occupational exposure. A minority of
patients develop emphysema as a result of alpha-1-protease inhibitor
deficiencyorintravenousdrugabuse.
B. The patient with acute exacerbations of COPD (AECOPD) usually will
complainofcough,sputumproduction,and/ordyspnea.Acuteexacerba-
tionsmaybeprecipitatedbyaninfectiousprocess,exposuretonoxious
stimuli,orenvironmentalchanges.Itisimportanttocomparethecurrent
illness with the severity of previous episodes and to determine if the
patienthashadpreviousintubationsoradmissionstotheICU.
C. Intercostalretractions,accessorymuscleuse,andanincreaseinpulsus
paradoxususuallysuggestsignificantairwayobstruction.
D. Wheezingisusuallypresent.Emphysemaismanifestedbyanelongated,
hyperresonantchest.Diaphragmaticflatteningandincreasedradiolucency
isseenonthechestx-ray.
ChronicObstructivePulmonaryDisease65
II. InfectiousprecipitantsofacuteexacerbationsofCOPD
A. About32%ofpatientswithanacuteexacerbationhaveaviralinfection.
The most common agents are influenza virus, parainfluenzae, and
respiratorysyncytialvirus.
B. Bacterial precipitants play an important etiologic role in AECOPD. H.
influenzaeisthemostcommonpathogen,occurringin19%,followedby
Streptococcus pneumoniae in 12% and Moraxella catarrhalis in 8%.
PatientswithCOPDhavechroniccolonizationoftherespiratorytreewith
Streptococcuspneumoniae,Haemophilusinfluenzae,andHaemophilus
parainfluenzae.
III. Diagnostictesting
A. Pulseoximetryisaninexpensive,noninvasiveprocedureforassessing
oxygensaturation.
B. Arterial blood gases. Both hypercarbia and hypoxemia occur when
pulmonaryfunctionfallstobelow25-30%ofthepredictednormalvalue.
C. Pulmonaryfunctiontestingisausefulmeansforassessingventilatory
function. Peak-flow meters are available that can provide a quick
assessmentofexpiratoryfunction.
D. ChestradiographywillpermitidentificationofpatientswithCOPDwith
pneumonia,pneumothorax,anddecompensatedCHF.
E. An ECG may be useful in patients who have a history of chest pain,
syncope,andpalpitations.
F. Labs: Complete blood count (CBC) is useful in patients with acute
exacerbation of COPD if pneumonia is suspected. The hematocrit is
frequently elevated as a result of chronic hypoxemia. A serum
theophylline level should be obtained in patients who are taking
theophylline.Eachmilligramperkilogramoftheophyllineraisestheserum
theophyllinelevelbyabout2mcg/mL.
IV. Pharmacotherapyforpatientstabilization
A. Oxygen. Patients in respiratory distress should receive supplemental
oxygentherapy.Oxygentherapyusuallyisinitiatedbynasalcannulato
maintainanO
2
saturation greater than 90%. Patients with hypercarbia
mayrequirecontrolledoxygentherapyusingaVenturimaskinorderto
achievemoreprecisecontroloftheFiO
2
.
B. Beta-agonistsarefirst-linetherapyforAECOPD.Albuterolisthemost
widelyusedagent.
Beta-AgonistDosages
Agent MDI Aerosol
Albuterol
(Proventil,Ventolin)
2-4puffsq4h 0.5cc(2.5mg)
Pirbuterol(Maxair) 2puffsq4-6h
Salmeterol(Serevent) 2puffsq12h
C. Anticholinergic agents produce preferential dilatation of the larger
centralairways,incontrasttobeta-agonists,whichaffecttheperipheral
airways.Ipratropiumis afirst-linetherapeuticoptionforchronic,outpatient
66ChronicObstructivePulmonaryDisease
managementofstablepatientswithCOPD.Theusualdoseis2-4puffs
every six hours.Theinhalationdoseis500mcg/2.5mL solutionnebulized
3-4timesdaily.
D. Corticosteroids.Rapidlytaperingcoursesofcorticosteroidsareeffective
inpreventingrelapsesandmaintaininglongersymptom-freeintervalsin
patientswhohavehadAECOPD. Patientswithanacuteexacerbationof
COPDshouldreceivesteroidsasamainstayofoutpatienttherapy.There
isnoroleforinhaledcorticosteroidsinthetreatmentofacuteexacerba-
tions.
1. Oral steroids are warranted in severe COPD. Prednisone 0.5-1.0
mg/kgor40mgqAM.Thedoseshouldbetaperedover1-2 weeks
followingclinicalimprovement.
2. Aerosolizedcorticosteroidsprovidethebenefitsoforalcorticosteroids
withfewersideeffects.
Triamcinolone(Azmacort)MDI2-4puffsbid.
Flunisolide(AeroBid,AeroBid-M)MDI2-4puffsbid.
Beclomethasone(Beclovent)MDI2-4puffsbid.
Budesonide(Pulmicort)MDI2puffsbid.
3. Sideeffectsofcorticosteroids.Cataracts,osteoporosis,sodiumand
waterretention,hypokalemia,muscleweakness,asepticnecrosisof
femoral and humeral heads, peptic ulcer disease, pancreatitis,
endocrineandskinabnormalities,musclewasting.
E. Theophyllinehasarelativelynarrowtherapeuticindexwithsideeffects
thatrangefromnausea,vomiting,andtremortomoreserioussideeffects,
including seizures and ventricular arrhythmias. Dosage of long-acting
theophylline (Slo-bid, Theo-Dur) is 200-300 mg bid. Theophylline
preparationswith24-houractionmaybeadministeredonceadayinthe
earlyevening.Theo-24,100-400mgqd[100,200,300,400mg].
F. Salmeterol(Serevent)isalong-actingbeta-agonist,whichmayimprove
nocturnaldyspneaandreducethefrequencyofbeta-agonistrescueuse.
2puffsq12h.
G. Summaryoftherapeuticapproaches
1. Acuteexacerbationsaretreatedwithsystemicsteroids,antibiotics,
and inhaled beta-agonists with combined ipratropium. Lack of
improvementshouldpromptadditionoftheophylline,salmeterol,non-
invasive ventilatory support (BIPAP), or intubation with mechanical
ventilatorysupport.
2. Chronic and stable COPD is treated with scheduled doses of
ipratropiumincombinationwithalbuterol.Salmeterolandtheophylline
are added when symptom control is difficult. Addition of an inhaled
steroid may be beneficial in selected patients. Continuous oxygen
therapy has clear benefits when indicated by a resting, exercise, or
sleepingPaO
2
<55mmHg.
H. Antibiotics.Amoxicillin-resistant,beta-lactamase-producingH.influenzae
are common. Azithromycin has an appropriate spectrum of coverage.
Levofloxacin is advantageous when gram-negative bacteria or atypical
organisms predominate. Amoxicillin-clavulanate has in vitro activity
againstbeta-lactamase-producingH.influenzaeandM.catarrhalis.
PleuralEffusion67
RecommendedDosingandDurationofAntibioticTherapyforAcute
ExacerbationsofCOPD
Mild-to-moderateacuteexacerbationsofCOPD
Azithromycin(Zithromax):500mgon1stday,250mgqd4daysor
clarithromycin(Biaxin)500mgPObid.
Amoxicillin/clavulanate(Augmentin):500mgtid10daysor
875mgbid10days.
SevereacuteexacerbationsofCOPD
Levofloxacin(Levaquin):500mgqd7-14days
Alternativeagentsfortreatmentofuncomplicated,acuteexacerba-
tionsofchronicbronchitis
Trimethoprim/sulfamethoxazole(Bactrim,Septra):1DStabPObid7-
14days
Amoxicillin(Amoxil,Wymox):500mgtid7-14days
Doxycycline(Vibramycin):100mgbid7-14days
V. Ventilatoryassistance
A. Patientswithextremedyspnea,discordantbreathing,fatigue,inabilityto
speak,ordeterioratingmentalstatusinthefaceofadequatetherapymay
require ventilatory assistance. Hypoxemia that does not respond to
oxygen therapy or worsening of acid-base status in spite of controlled
oxygentherapymayalsorequireventilatoryassistance.
B. Noninvasive,nasal,orbilevelpositiveairwaypressure(BiPAP)may
improverespiratoryrate,tidalvolume,andminuteventilation.Patients
successfullytreatedwithnoninvasiveventilationhavealowerincidence
ofpneumoniaandsinusitis.
VI. Surgical treatment. Lung volume reduction surgery (LVRS) consists of
surgicalremovalofanemphysematousbulla.Thisprocedurecanameliorate
symptomsandimprovepulmonaryfunction.Lungtransplantationisreserved
forthosepatientsdeemedunsuitableortooillforLVRS.
VII. Hypoxemiaadverselyaffectsfunctionandincreasesrisktheofdeath,and
oxygen therapy is the only treatment documented to improve survival in
patientswithCOPD.Oxygenisusuallydeliveredbynasalcannulaataflow
ratesufficienttomaintainanoptimaloxygensaturationlevel.
PleuralEffusion
Pre-thoracentesischestx-ray:Abilateraldecubitusx-rayshouldbeobtained
beforethethoracentesis.Thoracentesisissafewhenfluidfreelylayersout
andisgreaterthan10mmindepthonthedecubitusfilm.
Labs:CBC,ABG,SMA12,protein,albumin,amylase,rheumatoidfactor,ANA,
ESR. INR/PTT, UA. Chest x-ray PA & LAT repeat after thoracentesis,
bilateraldecubitus,ECG.
Pleuralfluidanalysis:
Tube1.LDH,protein,amylase,triglyceride,glucose(10mL).
68PleuralEffusion
Tube2.Gramstain,C&S,AFB,fungalC&S,(20-60mL,heparinized).
Tube3.Cellcountanddifferential(5-10mL,EDTA).
Tube 4. Antigen tests for S. pneumoniae, H. influenza (25-50 mL,
heparinized).
Syringe.pH(2mLcollectedanaerobically,heparinizedonice)
Bottle.Cytology.
DifferentialDiagnosis
PleuralFluidParam-
eters
Transudate Exudate
LDH(IU) <200 >200
PleuralLDH/serum
LDH
<0.6 >0.6
Totalprotein(g/dL) <3.0 >3.0
PleuralProtein/serum
Protein
<0.5 >0.5
DifferentialDiagnosisofTransudates:Congestiveheartfailure,cirrhosis.
Differential Diagnosis of Exudates: Empyema, viral pleuritis, tuberculosis,
neoplasm,uremia,drugreaction,asbestosis,sarcoidosis,collagendisease
(lupus,rheumatoiddisease),pancreatitis,subphrenicabscess.
ChylousEffusions:Triglyceride>110
MalignantEffusions:Cytologypositivein60%ofeffusions.
Treatment: Chesttubedrainageisindicated forcomplicatedparapneumonic
effusions (pH <7.10, glucose <40 mEq/dL, LDH >1000 IU/L) and frank
empyema.Rapidremovalmayrarelycausere-expansionpulmonaryedema.
References
Ferretti GR, et al. Acute pulmonary embolism; Role of helical CT in 164 patients with
intermediateprobabilityatventilation-perfusionscintigraphyandnormalresultsatduplex
USofthelegs.Radiology1997,205:453-458.
Kollefetal.TheAcuteRespiratoryDistresssyndrome.NEJM1995,332(1):27-37
Amatoetal.Effectofaprotective-ventilationstrategyonmortalityintheARDS.NEJM
1998,338(6)347-54
McIntyreNR.Clinicallyavailablenewstrategiesformechanicalventilatorysupport.Chest,
1993,104(2):500-5.
TobinMJ.MechanicalVentilation.NEJM,1994,330(15):1056-61
EstebanAetal.AComparisonoffourmethodsofweaningpatientsfrommechanical
ventilation.NEJM,1995,332(6):345-350.
TheColumbusInvestigators.Low-MolecularWeightHeparinintheTreatmentofpatients
withvenousthromboembolism.NEJM1997,337(10):657-662.
Pneumothorax69
Trauma
BlandingU.Jones,MD
Pneumothorax
I. Managementofpneumothorax
A. Smallprimaryspontaneouspneumothorax(<10-15%):(notassoci-
ated with underlying pulmonary diseases). If the patient is not
dyspneic.
1. Observefor4-8hoursandrepeatachestx-ray.
2. Ifthepneumothoraxdoesnotincreaseinsizeandthepatientremains
asymptomatic,considerdischargehomewithinstructionstorestand
curtailallstrenuousactivities.Thepatientshouldreturnifthereisan
increaseindyspneaorrecurrenceofchestpain.
B. Secondaryspontaneouspneumothorax(associatedwithunderlying
pulmonary pathology, emphysema) or primary spontaneous
pneumothorax>15%,orifpatientissymptomatic.
1. Givehigh-flowoxygenbynasalcannula.Aneedlethoracotomyshould
beplacedattheanterior,secondintercostalspaceinthemidclavicular
line.
2. Anesthetizeandprepthearea,theninserta16-gaugeneedlewithan
internalcatheteranda 60mLsyringe,attachedviaa3-waystopcock.
Aspirate until no more air is aspirated. If no additional air can be
aspirated, and the volume of aspirated air is <4 liters, occlude the
catheterandobservefor4hours.
3. Ifsymptomsabateandchest-x-raydoesnotshowrecurrenceofthe
pneumothorax,thecathetercanberemoved,andthepatientcanbe
dischargedhomewithinstructions.
4. Iftheaspiratedairis>4litersandadditionalairisaspiratedwithout
resistance, this represents an active bronchopleural fistula with
continuedairleak.Admissionisrequiredforinsertionofachesttube.
C. Traumatic pneumothorax associated with a penetrating injury,
hemothorax, mechanical ventilation, tension pneumothorax, or if
pneumothoraxdoesnotresolveafterneedleaspiration:Givehigh-
flowoxygenandinsertachesttube.Donotdelaythemanagementofa
tension pneumothorax until radiographic confirmation; insert needle
thoracotomyorchesttubeimmediately.
D. Iatrogenicpneumothorax
1. Iatrogenic pneumothoraces include lung puncture caused by
thoracentesisorcentrallineplacement.
2. Administeroxygenbynasalcannula.
3. Ifthepneumothoraxislessthan10%andthepatientisasymp-
tomatic, observe and repeat chest x-ray in 4 hours. If unchanged,
manageexpectantlywithclosefollow-up,andrepeatchestx-rayin24
hours.
4. If the pneumothorax is more than 10% and/or the patient is
symptomatic,performatubethoracostomyundernegativepressure.
70TensionPneumothorax
II. Techniqueofchesttubeinsertion
A. Placepatientinsupineposition,withinvolvedsideelevated20degrees.
Abduct the arm to 90 degrees. The usual site is the fourth or fifth
intercostal space, between the mid-axillary and anterior axillary line
(drainageofairorfreefluid).Thepointatwhichtheanterioraxillaryfold
meetsthechestwallisausefulguide.Alternatively,thesecondorthird
intercostalspace,inthemidclavicularline,maybeusedforpneumothorax
drainagealone(aironly).
B. Cleanse the skin with Betadine iodine solution, and drape the field.
Determinetheintrathoracic tubedistance(lateralchestwalltotheapices),
andmarkthelengthoftubewithaclamp.
C. Infiltrate 1% lidocaine into the skin, subcutaneous tissues, intercostal
muscles,periosteum,andpleurausinga25-gaugeneedle.Useascalpel
tomakeatransverseskinincision,2centimeterswide,locatedoverthe
rib,justinferiortotheinterspacewherethetubewillpenetratethechest
wall.
D. UseaKellyclamptobluntlydissectasubcutaneoustunnelfromtheskin
incision,extendingjustoverthesuperiormarginofthelowerrib.Avoidthe
nerve, artery and vein located at the upper margin of the intercostal
space.
E. Penetratethepleurawiththeclamp,andopenthepleura1centimeter.
Withaglovedfinger,explorethesubcutaneoustunnel,andpalpatethe
lung medially. Exclude possible abdominal penetration, and ensure
correct location within pleural space; use finger to remove any local
pleuraladhesions.
F. Use the Kelly clamp to grasp the tip of the thoracostomy tube (36 F,
internal diameter 12 mm), and direct it into the pleural space in a
posterior,superiordirectionforpneumothoraxevacuation.Directthetube
inferiorlyforpleuralfluidremoval.Guidethetubeintothepleuralspace
untilthelastholeisinsidethepleuralspaceandnotinsidethesubcutane-
oustissue.
G. Attachthetubetoaunderwatersealapparatuscontainingsterilenormal
saline,andadjustto20cmH
2
Oofnegativepressure,orattach tosuction
ifleakissevere.SuturethetubetotheskinofthechestwallusingOsilk.
ApplyVaselinegauze,4x4gauzesponges,andelastictape.Obtaina
chestx-raytoverifycorrectplacementandevaluatereexpansionofthe
lung.
TensionPneumothorax
I. Clinicalevaluation
A. Clinical signs: Severe hemodynamic and/or respiratory compromise;
contralaterallydeviatedtrachea;decreasedorabsentbreathsoundsand
hyperresonance to percussion on the affected side; jugular venous
distention,asymmetricalchestwallmotionwithrespiration.
B. Radiologic signs: Flattening or inversion of the ipsilateral
hemidiaphragm;contralateralshiftingofthemediastinum;flatteningofthe
cardio-mediastinal contour and spreading of the ribs on the ipsilateral
side.
CardiacTamponade71
II. Acutemanagement
A. Atemporarylarge-boreIVcathetermaybeinsertedintotheipsilateral
pleural space, at the level of the second intercostal space at the
midclavicularlineuntilthechesttubeisplaced.
B. Achesttubeshouldbeplacedemergently.
C. Draw blood for CBC, INR, PTT, type and cross-matching, chem 7,
toxicologyscreen.
D. Sendpleuralfluidforhematocrit,amylaseandpH(toruleoutesophageal
rupture).
E. Indications for cardiothoracic exploration: Severe or persistent
hemodynamicinstabilitydespiteaggressivefluidresuscitation,persistent
activebloodlossfromchesttube,morethan200cc/hrfor3consecutive
hours,or$1Lofacutebloodlossafterchesttubeplacement.
CardiacTamponade
I. Generalconsiderations
A. Cardiac tamponade occurs most commonly secondary to penetrating
injuries.
B. Beck'sTriad:Venouspressureelevation,dropinthearterialpressure,
muffledheartsounds.Othersignsincludeenlargedcardiacsilhouetteon
chest x-ray; signs and symptoms of hypovolemic shock; pulseless
electricalactivity,decreasedvoltageonECG.
C. Kussmaul's sign is characterized by a rise in venous pressure with
inspiration. Pulsus paradoxus or elevated venous pressure may be
absentwhenassociatedwithhypovolemia.
II. Management
A. Pericardiocentesisisindicatedifthepatientisunresponsivetoresuscita-
tionmeasuresforhypovolemicshock,orifthereisahighlikelihoodof
injurytothemyocardiumoroneofthegreatvessels.
B. All patients who have a positive pericardiocentesis (recovery of non-
clotting blood) because of trauma, require an open thoracotomy with
inspectionofthemyocardiumandthegreatvessels.
C. Rule out other causes of cardiac tamponade such as pericarditis,
penetrationofcentrallinethroughthevenacava,atrium,orventricle,or
infection.
D. Considerother causes of hemodynamicinstabilitythatmaymimiccardiac
tamponade(tensionpneumothorax,massivepulmonaryembolism,shock
secondarytomassivehemothorax).
Pericardiocentesis
I. Generalconsiderations
A. If acute cardiac tamponade with hemodynamic instability is suspected,
emergencypericardiocentesisshouldbeperformed;infusionofRinger's
lactate, crystalloid, colloid and/or blood may provide temporizing mea-
sures.
72Pericardiocentesis
II. Management
A. Protect airway and administer oxygen. If patient can be stabilized,
pericardiocentesisshouldbeperformedintheoperatingroomorcatheter
lab.Thepara-xiphoidapproachisusedforpericardiocentesis.
B. Placepatientinsupinepositionwithchestelevatedat30-45degrees,
then cleanse and drape peri-xiphoid area. Infiltrate lidocaine 1% with
epinephrine(iftimepermits)intoskinanddeeptissues.
C. Attachalong,largebore(12-18cm,16-18gauge),shortbevelcardiac
needletoa50ccsyringewitha3-waystopcock.Useanalligatorclipto
attachaV-leadoftheECGtothemetaloftheneedle.
D. Advancetheneedlejustbelowcostalmargin,immediatelytotheleftand
inferiortothexiphoidprocess.Applysuctiontothesyringewhileadvanc-
ingtheneedleslowlyata45-degreehorizontalangletowardsthemid
pointoftheleftclavicle.
E. Astheneedlepenetratesthepericardium,resistancewillbefelt,anda
poppingsensationwillbenoted.
F. MonitortheECGforSTsegmentelevation(indicatingventricularheart
muscle contact); or PR segment elevation (indicating atrial epicardial
contact). Aftertheneedlecomesincontactwiththeepicardium,withdraw
theneedleslightly.Ectopicventricularbeatsareassociatedwithcardiac
penetration.
G. Aspirate as much blood as possible. Blood from the pericardial space
usuallywillnotclot. Blood,inadvertently,drawnfrominsidetheventricles
oratriumusuallywillclot.Iffluidisnotobtained,redirecttheneedlemore
towardsthehead.StabilizetheneedlebyattachingahemostatorKelly
clamp.
H. Consider emergency thoracotomy to determine the cause of
hemopericardium (especiallyif active bleeding). If the patient does not
improve,considerotherproblemsthatmayresemble tamponade,suchas
tension pneumothorax, pulmonary embolism, or shock secondary to
massivehemothorax.
References
CommitteeonTrauma,AmericanCollegeofSurgeons:EarlyCareoftheInjuredPatient.
Philadelphia,WBSandersCo.,1982,pp142-148.
LightRW. ManagementofSpontaneousPneumothorax. Am.Rev.Res.Dis.1993;148,1:
245-248.
Light RW. Pneumothorax. In: Light RW, ed. Pleural Diseases. Philadelphia; Lea &
Farbiger,1990;237-62.
TransfusionReactions73
Hematologic Disorders
ThomasVovan,MD
TransfusionReactions
I. Acutehemolytictransfusionreaction
A. TransfusionreactionsarerareandmostcommonlyassociatedwithABO
incompatibility,usuallyrelatedtoaclericalerror.Earlysymptomsinclude
suddenonsetofanxiety,flushing,tachycardia,andhypotension.Chest
andbackpain,fever,anddyspneaarecommon.
B. Life-threateningmanifestationsincludevascularcollapse(shock),renal
failure,bronchospasm,anddisseminatedintravascularcoagulation.
C. Hemoglobinuria,andhemoglobinemiaoccursbecauseofintravascular
redcelllysis.
D. Thedirectantiglobulintest(directCoombstest)ispositive.Theseverity
ofreactionisusuallyrelatedtothevolumeofRBCsinfused.
E. Management
1. Thetransfusionshouldbediscontinuedimmediately,andtheunused
donorbloodandasampleofrecipientsvenousbloodshouldbesent
forretypingandrepeatcrossmatch,includingadirect andindirect
Coombstest.
2. Urineanalysisshouldbecheckedforfreehemoglobinandcentrifuged
plasmaforpinkcoloration(indicatingfreehemoglobin).
3. Hypotensionshouldbetreatedwithnormalsaline.Vasopressorsmay
beusedifvolumereplacementaloneisinadequatetomaintainblood
pressure.
4. Maintain adequate renal perfusion with volume replacement.
Furosemide may be used to maintain urine output after adequate
volumereplacementhasbeenachieved.
5. MonitorINR/PTT,platelets,fibrinogen,andfibrindegradationproducts
for evidence of disseminated intravascular coagulation. Replace
required clotting factors with fresh frozen plasma, platelets, and/or
cryoprecipitate.
II. Febriletransfusionreaction(nonhemolytic)
A. Febriletransfusionreactionsoccurin0.5-3%oftransfusions.Itismost
commonlyseeninpatientsreceivingmultipletransfusions.Chillsdevelop,
followedbyfever,usuallyduringorwithinafewhoursoftransfusion.This
reactionmaybeseverebutisusuallymildandselflimited.
B. Management
1. Symptomatic and supportive care should be provided with
acetaminophenanddiphenhydramine.Meperidine50mgIVisuseful
intreatingchills.AWBCfiltershouldbeusedfortheanysubsequent
transfusions.
2. More serious transfusion reactions must be excluded (eg, acute
hemolyticreactionorbacterialcontaminationofdonorblood).
III. Transfusion-relatednoncardiogenicpulmonaryedema
A. This reaction is characterized by sudden development of severe
respiratory distress, associated with fever, chills, chest pain, and
hypotension.
74DisseminatedIntravascularCoagulation
B. Chestradiographdemonstratesdiffusepulmonaryedema.Thisreaction
maybesevereandlifethreateningbutgenerallyresolveswithin48hours.
C. Management
1. Treatmentofpulmonaryedemaandhypoxemiamayincludemechani-
calventilatorysupportandhemodynamicmonitoring.
2. Diureticsareusefulonlyiffluidoverloadispresent.UseaWBCfilter
shouldbeusedforanysubsequenttransfusions.
DisseminatedIntravascularCoagulation
I. Clinicalmanifestations
A. Disseminatedintravascularcoagulation(DIC)ismanifestbygeneralized
ecchymosis and petechiae, bleeding from peripheral IV sites, central
catheters,surgicalwounds,andoozingfromgums.
B. Gastrointestinal and urinary tract bleeding are frequently encountered.
Grayishdiscolorationorcyanosisofthedistalfingers,toes,orearsmay
occurbecauseofintravascularthrombosis.Large,sharplydemarcated,
ecchymoticareasmaybeseenasaresultofthrombosis.
II.Diagnosis
A. FibrindegradationproductsarethemostsensitivescreeningtestforDIC;
however,nosinglelaboratoryparameterisdiagnosticofDIC.
B. Peripheral smear: Evidence of microangiopathic hemolysis, with
schistocytesandthrombocytopenia,isoftenpresent.Apersistentlynormal
plateletcountnearlyexcludesthediagnosisofacuteDIC.
C. Coagulation studies: INR, PTT, and thrombin time are generally
prolonged. Fibrinogen levels are usually depleted (<150 mg/dL). Fibrin
degradationproducts(>10mg/dL)andD-dimeriselevated(>0.5mg/dL).
III. Managementofdisseminatedintravascularcoagulation
A. The primary underlying precipitating condition (eg, sepsis) should be
treated.SevereDICwithhypocoagulabilitymaybetreatedwithreplace-
mentofclottingfactors.Hypercoagulabilityismanagedwithheparin.
B. Severehemorrhageandshockismanagedwithfluidsandredbloodcell
transfusions.
C. IfthepatientisathighriskofbleedingoractivelybleedingwithDIC:
Replacefibrinogenwith10unitsofcryoprecipitate.Replaceclottingfactors
with 2-4 units of fresh frozen plasma. Replace platelets with platelet
pheresis.
D. If factor replacement therapy is transfused, fibrinogen and platelet
levelsshouldbeobtained30-60minutespost-transfusionandevery4-6
hoursthereaftertodeterminetheefficacyoftherapy.Eachunitofplatelets
should increase the platelet count by 5000-10,000/mcL. Each unit of
cryoprecipitateshouldincreasethefibrinogenlevelby5-10mg/dL.
E. Heparin
1. Indicationsforheparinincludeevidenceoffibrindeposition(ie,dermal
necrosis,acralischemia,venousthromboembolism).Heparinisused
whenthecoagulopathyisbelievedtobesecondarytoaretained,dead
fetus,amnioticfluidembolus,gianthemangioma,aorticaneurysm,solid
tumors,orpromyelocyticleukemia.Heparinisalsousedwhenclotting
factorscannotbecorrectedwithreplacementtherapyalone.
2. Heparintherapyisinitiatedatarelativelylowdose(5-10U/kg/hr)by
continuousIVinfusionwithoutabolus.Coagulationparametersmust
Thrombolytic-associatedBleeding75
thenbefollowedtoguidetherapy.Theheparindosemaybeincreased
by2.5U/kg/hruntilthedesiredeffectisachieved.
Thrombolytic-associatedBleeding
I. Clinicalpresentation:Post-fibrinolysishemorrhagemaypresentasasudden
neurologic deficit (intracranial bleeding), massive GI bleeding, progressive
back pain accompanied by hypotension (retroperitoneal bleeding), or a
gradualdeclineinhemoglobinwithoutovertevidenceofbleeding.
II.Laboratoryevaluation
A. Low fibrinogen (<100 mg/dL) and elevated fibrin degradation products
confirmthepresenceofalyticstate.ElevatedthrombintimeandPTTmay
suggest a persistent lytic state; however, both are prolonged in the
presenceofheparin.Prolongedreptilasetimeidentifiesthepersistentlytic
stateinthepresenceofheparin.
B. Depletedfibrinogeninthefibrinolyticstatewillbereflectedbyanelevated
PTT,thrombintime,orreptilasetime.Thepost-transfusionfibrinogenlevel
isausefulindicatorofresponsetoreplacementtherapy.
C. Thebleedingtimemaybeahelpfulguidetoplateletreplacementtherapy
if the patient has persistent bleeding despite factor replacement with
cryoprecipitateandfreshfrozenplasma.
III. Management
A. Discontinuethrombolytics,aspirin,andheparinimmediately,andconsider
protaminereversalofheparinandcryoprecipitatetoreplenishfibrinogen.
B. Place two large-bore IV catheters for volume replacement. If possible,
applylocalpressuretobleedingsites.Bloodspecimensshouldbesentfor
INR/PTT, fibrinogen,andthrombintime.Reptilasetimeshouldbechecked
ifthepatientisalsoreceivingheparin.Patient'sbloodshouldbetypedand
crossedbecauseurgenttransfusionmaybeneeded.
C. Transfusion
1. Cryoprecipitate (10 units over 10 minutes) should be transfused to
correctthelyticstate.Transfusionsmayberepeateduntilthefibrinogen
levelisabove100mg/dLorhemostasisisachieved.Cryoprecipitateis
richinfibrinogenandfactorVIII.
2. Freshfrozenplasmatransfusionisalsoimportantforreplacementof
factor VIII and V. If bleeding persists after cryoprecipitate and FFP
replacement,checkableedingtimeandconsiderplatelettransfusion
ifbleedingtimeisgreaterthan9minutes.Ifbleedingtimeislessthan
9minutes,thenantifibrinolyticdrugsmaybewarranted.
D. Antifibrinolyticagents
1. Aminocaproicacid(EACA)inhibitstheconversionofplasminogento
plasmin. It is used when replacement of blood products are not
sufficienttoattainhemostasis.
2. Loadingdose:5gor0.1g/kgIVinfusedin250ccNSover30-60min,
followed by continuous infusion at 0.5-2.0 g/h until bleeding is con-
trolled.Usewithcautioninupperurinarytractbleedingbecauseofthe
potentialforobstruction.
References
CarrJM,McKinneyM,McDonaghJ:DiagnosisofDisseminatedIntravascularCoagulation,
RoleofD-Dimer.AmJClinPathol1989;91:280-287.
76Thrombolytic-associatedBleeding
FeinsteinDI:TreatmentofDisseminatedIntravascularCoagulation.SeminarsinThrombosis
andHemostasis.1988;14:351-362.
Sane DC, Califf RM, Topol EJ, Stump DC, Mark DB, Greenberg CS: Bleeding during
ThrombolyticTherapyforAcuteMyocardialInfarction:MechanismsandManagement.
AnnofIntMed.1989;111:1010-1022.
BacterialMeningitis77
Infectious Diseases
GuyFoster,MD
FarhadMazdisnian,MD
MichaelKrutzik,MD
GeorginaHeal,MD
BacterialMeningitis
The age group at greatest risk for acute bacterial meningitis (ABM) includes
childrenbetween1and24monthsofage.Adults olderthan60yearsoldaccount
for50%ofalldeathsrelatedtomeningitis.
I. Clinicalpresentation
A. Eighty-fivepercentofpatientswithbacterialmeningitispresentwithfever,
headache, meningismus or nuchal rigidity, and altered mental status.
Othercommonsignsandsymptomsincludephotophobia,vomiting,back
pain,myalgias,diaphoresis,andmalaise.Generalizedseizurescanoccur
inupto40%ofpatientswithABM.
B. Kernig'ssign(resistancetoextensionofthelegwhilethehipisflexed)and
Brudzinski'ssign(involuntaryflexionofthehipandkneewhenthepatient's
neckisabruptlyflexedwhilelayingsupine)areobservedinupto50%of
patients.
C. About 50% of patients with N. meningitidis may present with an
erythematousmacularrash,whichprogressestopetechiaeandpurpura.
II. Patientevaluation
A. Computerizedtomography(CT). PatientswhorequireCTpriortoLP
includethosewithfocalneurologicfindings,papilledema,focalseizures,
orabnormalitiesonexamthatsuggestincreasedintracranialpressure.If
bacterialmeningitisisastrongconsideration,andthedecisionismadeto
performaCTpriortoLP,twosetsofbloodculturesshouldbeobtained
and antibiotics should be administered before sending the patient for
neuroimaging.Urineculturesmaybehelpfulintheveryyoungandvery
old.
B. Bloodculturesfollowedbyantibioticadministrationwithin30minutesof
presentation is mandatory in all patients suspected of having bacterial
meningitis.
C. Interpretationoflumbarpuncture.ExaminationoftheCSFismandatory
forevaluationofmeningitis.
D. CSF, Grams stain, and culture are positive in 70-85% of patients with
ABM.
78BacterialMeningitis
CerebrospinalFluidParametersinMeningitis
Normal Bacterial Viral Fungal TB Para-
menin-
geal
Focus
orAb-
scess
WBC
count
(WBC/
:L)
0-5 >1000 100-
1000
100-500 100-
500
10-1000
%PMN 0-15 90 <50 <50 <50 <50
%
lymph
>50 >50 >80
Glucose
(mg/
dL)
45-65 <40 45-
65
30-45 30-
45
45-65
CSF:
blood
glucose
ratio
0.6 <0.4 0.6 <0.4 <0.4 0.6
Protein
(mg/dL)
20-45 >150 50-
100
100-500 100-
500
>50
Open-
ing
press-
ure
(cm
H
2
0)
6-20 >180mm
H
2
0
NLor
+
>180
mmH
2
0
>180
mm
H
2
0
N/A
E. IftheCSFparametersarenondiagnostic,orthepatienthasbeentreated
withpriororalantibiotics,and,therefore,theGram'sstainand/orculture
arelikelytobenegative,thenlatexagglutination(LA)maybehelpful.The
testhasavariablesensitivityrate,rangingbetween50-100%,andhigh
specificity. Latex agglutination tests are available for H. influenza,
Streptococcuspneumoniae,N.meningitidis,EscherichiacoliK1,andS.
agalactiae(GroupBstrep).CSFCryptococcalantigenandIndiainkstain
should be considered in patients who have HIV disease or HIV risk
factors.
BacterialMeningitis79
III. Treatmentofacutebacterialmeningitis
AntibioticChoiceBasedonAgeandComorbidMedicalIllness
Age Organism Antibiotic
Neonate E.coli,GroupBstrep,
Listeriamonocytogenes
Ampicillinandceftriaxone
orcefotaxime
1-3months S.pneumoniae,N.
meningitidis,H.
influenzae,S.agalactiae,
Listeria,E.coli
Ceftriaxoneorcefotaxime
andvancomycin
3monthsto18years N.meningitidis,S.
pneumoniae,H.
influenzae
Ceftriaxoneorcefotaxime
andvancomycin
18-50years S.pneumoniae,N.
meningitidis
Ceftriaxoneorcefotaxime
andvancomycin
Olderthan50years N.meningitidis,S.
pneumoniae
Gram-negativebacilli,Lis-
teria,GroupBstrep
Ampicillinandceftriaxone
orcefotaximeand
vancomycin
Neurosurgery/head
injury
S.aureus,S.epidermidis
Diphtheroids,Gram-nega-
tivebacilli
Vancomycinand
Ceftazidime
Immunosuppression Listeria,Gram-negative
bacilli,S.pneumoniae,N.
meningitidis
AmpicillinandCeftazidime
(consideradding
Vancomycin)
CSFshunt S.aureus,Gram-negative
bacilli
Vancomycinand
Ceftazidime
AntibioticChoiceBasedonGramsStain
StainResults Organism Antibiotic
Gram's(+)cocci S.pneumoniae
S.aureus,S.agalactiae
(GroupB)
Vancomycinand
ceftriaxoneorcefotaxime
Gram's(-)cocci N.meningitidis PenicillinGor
chloramphenicol
Gram's(-)coccobacilli H.influenzae Third-generation
cephalosporin
80BacterialMeningitis
StainResults Organism Antibiotic
Gram's(+)bacilli Listeriamonocytogenes Ampicillin,PenicillinG+
IVGentamicin
intrathecalgentamicin
Gram's(-)bacilli E.coli,Klebsiella
Serratia,Pseudomonas
Ceftazidime+/-
aminoglycoside
RecommendedDosagesofAntibiotics
Antibiotic Dosage
Ampicillin 2gIVq4h
Cefotaxime 2gIVq4-6h
Ceftazidime 2gIVq8h
Ceftriaxone 2gIVq12h
Chloramphenicol 0.5-1.0gmIVq6h
Gentamicin Load2.0mg/kgIV,then1.5mg/kg
q8h
Nafcillin/Oxacillin 2gIVq4h
PenicillinG 4millionunitsIVq4h
Rifampin 600mgPOq24h
Trimethoprim-sulfamethoxazole 15mg/kgIVq6h
Vancomycin 1.0-1.5gIVq12h
A. Inareascharacterizedbyhighresistancetopenicillin,vancomycinplus
a third-generation cephalosporin should be the first-line therapy. H.
influenzae is usually adequately covered by a third-generation
cephalosporin. The drug of choice for N. meningitidis is penicillin or
ampicillin. Chloramphenicol should be used if the patient is allergic to
penicillin. Aztreonam may be used for gram-negative bacilli, and
trimethoprim-sulfamethoxazolemaybeusedforListeria.
B. In patients who are at risk for Listeria meningitis, ampicillin must be
addedtotheregimen.S.agalactiae(GroupB)iscoveredbyampicillin,
and adding an aminoglycoside provides synergy. Pseudomonas and
otherGram-negativebacillishouldbetreatedwithabroadspectrumthird-
generation cephalosporin (ceftazidime) plus an aminoglycoside. S.
aureusmaybecoveredbynafcillinoroxacillin.High-dosevancomycin
(peak 35-40 mcg/mL) may be needed if the patient is at risk for
methicillin-resistantS.aureus.
Pneumonia81
C. Corticosteroids.Audiologicandneurologicalsequelaeininfantsolder
thantwomonthsofagearemarkedlyreducedbyearlyadministrationof
dexamethasoneinpatientswithH.influenzae meningitis.Dexametha-
sone should be given at a dose of 0.15 mg/kg q6h IV for2-4daysto
childrenwithsuspectedH.influenzaeorpneumococcalmeningitis.The
doseshouldbegivenjustpriortoorwiththeinitiationofantibiotics.
Pneumonia
Community-acquiredpneumoniaistheleadinginfectiouscauseofdeathandis
thesixth-leadingcauseofdeathoverall.
I. Clinicaldiagnosis
A. Symptomsofpneumoniamayincludefever,chills,malaiseandcough.
Patientsalsomayhavepleurisy,dyspnea,orhemoptysis.Eightypercent
ofpatientsarefebrile.
B. Physical exam findings may include tachypnea, tachycardia, rales,
rhonchi,bronchialbreathsounds,anddullnesstopercussionoverthe
involvedareaoflung.
C. Chestradiographusuallyshowsinfiltrates.Thechestradiographmay
revealmultilobarinfiltrates,volumeloss,orpleuraleffusion.Thechest
radiographmaybenegative veryearlyintheillnessbecauseofdehy-
drationorsevereneutropenia.
D. Additionaltestingmayincludeacompletebloodcount,pulseoximetry
orarterialbloodgasanalysis.
II. Laboratoryevaluation
A. SputumforGramstainandcultureshouldbeobtainedinhospitalized
patients. In a patient who has had no prior antibiotic therapy, a high-
qualityspecimen(>25whitebloodcellsand<5epithelialcells/hpf)may
helptodirectinitialtherapy.
B. Bloodculturesarepositivein11%ofcases,andculturesmayidentify
aspecificetiologicagent.
C. Serologic testing for HIV is recommended in hospitalized patients
between the ages of 15 and 54 years. Urine antigen testing for
legionella is indicated in endemic areas for patients with serious
pneumonia.
III. Indicationsforhospitalization
A. Age>65years
B. Unstable vital signs (heart rate >140 beats per minute, systolic blood
pressure<90mmHg,respiratoryrate>30beatsperminute)
C. Alteredmentalstatus
D. Hypoxemia(PO
2
<60mmHg)
E. Severeunderlyingdisease(lungdisease,diabetesmellitus,liverdisease,
heartfailure,renalfailure)
F. Immunecompromise(HIVinfection,cancer,corticosteroiduse)
G. Complicatedpneumonia(extrapulmonaryinfection,meningitis,cavitation,
multilobarinvolvement,sepsis,abscess,empyema,pleuraleffusion)
H. Severe electrolyte, hematologic or metabolic abnormality (ie, sodium
<130mEq/L,hematocrit<30%,absoluteneutrophilcount<1,000/mm
3
,
serumcreatinine>2.5mg/dL)
I. Failuretorespondtooutpatienttreatmentwithin48to72hours.
82Pneumonia
PathogensCausingCommunity-AcquiredPneumonia
MoreCommon LessCommon
Streptococcuspneumoniae
Haemophilusinfluenzae
Moraxellacatarrhalis
Mycoplasmapneumoniae
Chlamydiapneumoniae
Legionellaspecies
Viruses
Anaerobes(especiallywithaspiration)
Staphylococcusaureus
Gram-negativebacilli
Pneumocystiscarinii
Mycobacteriumtuberculosis
IV. Treatmentofcommunity-acquiredpneumonia
RecommendedEmpiricDrugTherapyforPatientswithCommunity-
AcquiredPneumonia
ClinicalSituation PrimaryTreatment Alternative(s)
Younger(<60yr)out-
patientswithoutun-
derlyingdisease
Macrolideantibiotics
(azithromycin,
clarithromycin,
dirithromycin,or
erythromycin)
Levofloxacinordoxycycline
Older(>60yr)outpa-
tientswithunderlying
disease
Levofloxacinor
cefuroximeor
Trimethoprim-sulfa-
methoxazole
Addvancomycinin
severe,life-threaten-
ingpneumonias
Beta-lactamaseinhibitor(with
macrolideiflegionellainfec-
tionsuspected)
Grossaspirationsus-
pected
ClindamycinIV Cefotetan,
ampicillin/sulbactam
A. Younger,otherwisehealthyoutpatients
1. The most commonly identified organisms in this group are S
pneumoniae, M pneumoniae, C pneumoniae, andrespiratoryviruses.
2. Erythromycin has excellent activity against most of the causal
organismsinthisgroupexcept H influenzae.
3. The newer macrolides, active against H influenzae (azithromycin
[Zithromax] and clarithromycin [Biaxin]), are effective as empirical
monotherapyforyoungeradultswithoutunderlyingdisease.
B. Olderoutpatientswithunderlyingdisease
1. The most common pathogens in this group are S pneumoniae, H
influenzae, respiratoryviruses,aerobicgram-negativebacilli,andS
aureus. AgentssuchasM pneumoniae andCpneumoniae arenot
usually found in this group. Pseudomonas aeruginosa is rarely
identified.
Pneumonia83
2. A second-generation cephalosporin (eg, cefuroxime [Ceftin]) is
recommended for initial empirical treatment. Trimethoprim-
sulfamethoxazoleisaninexpensivealternativewherepneumococcal
resistancetonotprevalent.
3. Whenlegionellainfectionissuspected,initialtherapyshouldinclude
treatmentwithamacrolideantibioticinadditiontoabeta-lactam/beta-
lactamaseinhibitor(amoxicillinclavulanate).
C. Moderatelyill,hospitalizedpatients
1. InadditiontoSpneumoniae andH influenzae, morevirulentpatho-
gens,suchasSaureus, Legionella species,aerobicgram-negative
bacilli(includingP aeruginosa, andanaerobes),shouldbeconsidered
inpatientsrequiringhospitalization.
2. Hospitalized patients should receive an intravenous cephalosporin
active against S pneumoniae and anaerobes (eg, cefuroxime,
ceftriaxone[Rocephin],cefotaxime[Claforan]),orabeta-lactam/beta-
lactamaseinhibitor.
3. Nosocomialpneumoniashouldbesuspectedinpatientswithrecent
hospitalizationornursinghomestatus.Nosocomialpneumoniaismost
commonlycausedbyPseudomonasorStaphaureus.Empirictherapy
shouldconsistofvancomycin anddoublepseudomonalcoveragewith
a beta-lactam (cefepime, Zosyn, imipenem, ticarcillin, ceftazidime,
cefoperazone) and an aminoglycoside (amikacin, gentamicin,
tobramycin)oraquinolone(ciprofloxacin).
4. When legionella is suspected (in endemic areas, cardiopulmonary
disease,immunecompromise),amacrolideshouldbeaddedtothe
regimen. If legionella pneumonia is confirmed, rifampin (Rifadin)
shouldbeaddedtothemacrolide.
CommonAntimicrobialAgentsforCommunity-AcquiredPneumonia
inAdults
Type Agent Dosage
Oraltherapy
Macrolides Erythromycin
Clarithromycin(Biaxin)
Azithromycin(Zithromax)
500mgPOqid
500mgPObid
500mgPOonday1,then
250mgqdx4days
Beta-lactam/beta-
lactamaseinhibitor
Amoxicillin-clavulanate
(Augmentin)
500mgtidor875mgPO
bid
Quinolones Ciprofloxacin(Cipro)
Levofloxacin(Levaquin)
Ofloxacin(Floxin)
500mgPObid
500mgPOqd
400mgPObid
Tetracycline Doxycycline 100mgPObid
Sulfonamide Trimethoprim-
sulfamethoxazole
160mg/800mg(DS)PO
bid
84Pneumonia
Type Agent Dosage
IntravenousTherapy
Cephalosporins
Second-generation
Third-generation
(anti-Pseudomonas
aeruginosa)
Cefuroxime(Kefurox,
Zinacef)
Ceftizoxime(Cefizox)
Ceftazidime(Fortaz)
Cefoperazone(Cefobid)
0.75-1.5gIVq8h
1-2gIVq8h
1-2gIVq8h
1-2gIVq8h
Beta-lactam/beta-
lactamaseinhibitors
Ampicillin-sulbactam
(Unasyn)
Piperacillin/tazobactam
(Zosyn)
Ticarcillin-clavulanate
(Timentin)
1.5gIVq6h
3.375gIVq6h
3.1gIVq6h
Quinolones Ciprofloxacin(Cipro)
Levofloxacin(Levaquin)
Ofloxacin(Floxin)
400mgIVq12h
500mgIVq24h
400mgIVq12h
Aminoglycosides Gentamicin
Amikacin
Load2.0mg/kgIV,then
1.5mg/kgq8h
Vancomycin Vancomycin 1gmIVq12h
D.Criticallyillpatients
1. Spneumoniae andLegionella speciesarethemostcommonlyisolated
pathogens, andaerobicgram-negativebacilliareidentifiedwithincreas-
ingfrequency. Mpneumoniae,respiratoryviruses,andHinfluenzaeare
lesscommonlyidentified.
2. Erythromycin should be used along with an antipseudomonal agent
(ceftazidime,imipenem-cilastatin[Primaxin],orciprofloxacin[Cipro]).
An aminoglycoside should be added for additional antipseudomonal
activityuntilcultureresultsareknown.
3. Severe life-threatening community-acquired pneumonias should be
treated with vancomycin empirically until culture results are known.
Twenty-fivepercentofS.pneumoniaeisolatesarenolongersuscepti-
ble to penicillin, and 9% are no longer susceptible to extended-
spectrumcephalosporins.
4. Pneumonia caused by penicillin-resistant strains of S. pneumoniae
should be treated with high-dose penicillin G (2-3 MU IV q4h), or
cefotaxime(2gmIVq8h),orceftriaxone(2gmIVq12h),ormeropenem
(Merrem)(500-1000mgIVq8h),orvancomycin(Vancocin)(1gmIV
q12h).
5. H.influenzaeandMoraxellacatarrhalisoftenproducebeta-lactamase
enzymes,makingtheseorganismsresistanttopenicillinandampicillin.
Infection with these pathogens is treated with a second-generation
cephalosporin,beta-lactam/beta-lactamaseinhibitorcombinationsuch
as amoxicillin-clavulanate, azithromycin, or trimethoprim-sulfameth-
oxazole.
PneumocystisCariniiPneumonia85
6. Mostbacterialinfectionscanbeadequatelytreatedwith10-14daysof
antibiotictherapy.Mpneumoniae and C pneumoniae infectionsrequire
treatmentforupto14days.Legionellainfectionsshouldbetreatedfor
aminimumof14days;immunocompromisedpatientsrequire21days
oftherapy.
PneumocystisCariniiPneumonia
PCP is the most common life-threatening opportunistic infection occurring in
patients with HIV disease. In the era of PCP prophylaxis and highly active
antiretroviraltherapy,theincidenceofPCPisdecreasing.TheincidenceofPCP
hasdeclinedsteadilyfrom50%in1987to25%currently.
I. RiskfactorsforPneumocystiscariniipneumonia
A.PatientswithCD4countsof200cells/Lorlessare4.9timesmorelikely
todevelopPCP.
B.CandidatesforPCPprophylaxisinclude:patientswithapriorhistoryof
PCP,patientswithaCD4cellcountoflessthan200cells/L,andHIV-
infectedpatientswiththrushorpersistentfever.
II. Clinicalpresentation
A.PCPusuallypresentswithfever,drycough,andshortnessofbreathor
dyspneaonexertionwithagradualonsetoverseveralweeks.Tachypnea
maybepronounced.Circumoral,acral, andmucousmembranecyanosis
maybeevident.
B.Laboratoryfindings
1. Completebloodcountandsedimentationrateshowsnocharacter-
istic pattern in patients with PCP. The serum LDH concentration is
frequentlyincreased.
2. ArterialbloodgasmeasurementsgenerallyshowincreasesinP(A-
a)O
2
, although PaO
2
values vary widely depending on disease
severity. Up to 25% of patients may have a PaO
2
of 80 mm Hg or
abovewhilebreathingroomair.
3. Pulmonary function tests. Patients with PCP usually have a
decreaseddiffusingcapacityforcarbonmonoxide(DLCO).
C.Radiographicpresentation
1. PCPinAIDSpatientsusuallycausesadiffuseinterstitialinfiltrate.High
resolutioncomputerizedtomography(HRCT)maybehelpfulforthose
patientswhohavenormalchestradiographicfindings.
2. Pneumatoceles (cavities, cysts, blebs, or bullae) and spontaneous
pneumothoracesarecommoninpatientswithPCP.
III. Laboratorydiagnosis
A.Sputuminduction.Theleastinvasivemeansofestablishingaspecific
diagnosisistheexaminationofsputuminducedbyinhalationofa3-5%
salinemist.ThesensitivityofinducedsputumexaminationforPCPis74-
77%andthenegativepredictivevalueis58-64%.Ifthesputum tests
negative, an invasive diagnostic procedure is required to confirm the
diagnosisofPCP.
B.Transbronchialbiopsyandbronchoalveolarlavage.Thesensitivityof
transbronchialbiopsyforPCPis98%.Thesensitivityofbronchoalveolar
is90%.
86Pneumonia
C.Open-lung biopsy should be reserved for patients with progressive
pulmonary disease in whom the less invasive procedures are
nondiagnostic.
IV. Diagnosticalgorithm
A.Ifthechestradiographofasymptomaticpatientappearsnormal,aDLCO
should be performed. Patients with significant symptoms, a normal-
appearingchestradiograph,andanormalDLCOshouldundergohigh-
resolution CT. Patients with abnormal findings at any of these steps
shouldproceedtosputuminductionorbronchoscopy.Sputumspecimens
collected by induction that reveal P. carinii should also be stained for
acid-fastorganismsandfungi,andthespecimenshouldbeculturedfor
mycobacteriaandfungi.
B.PatientswhosesputumexaminationsdonotshowP.cariniioranother
pathogenshouldundergobronchoscopy.
C.LavagefluidisstainedforP.carinii,acid-fastorganisms,andfungi.Also,
lavagefluidisculturedformycobacteriaandfungiandinoculatedonto
cell culture for viral isolation. Touch imprints are made from tissue
specimens andstainedforP.carinii.Fluidisculturedformycobacteria
andfungi,andstainedforP.carinii,acid-fastorganisms,andfungi.Ifall
proceduresarenondiagnosticandthelungdiseaseisprogressive,open-
lungbiopsymaybeconsidered.
V. Therapyandprophylaxis
A.Trimethoprim-sulfamethoxazoleDS(BactrimDS,SeptraDS)isthe
recommendedinitialtherapyforPCP. Dosageis15-20mg/kg/dayofTMP
IV divided q6h for 14-21 days. Adverse effects include rash (33%),
elevationofliverenzymes(44%),nauseaandvomiting(50%),anemia
(40%),creatinineelevation(33%),andhyponatremia(94%).
B.Pentamidineisanalternativeinpatientswhohaveadversereactionsor
fail to respond to TMP-SMX. The dosage is 4 mg/kg/day IV for 14-21
days.Adverseeffectsincludeanemia(33%),creatinineelevation(60%),
LFT elevation (63%), and hyponatremia (56%). Pancreatitis, hypo-
glycemia,andhyperglycemiaarecommonsideeffects.
C.Corticosteroids. Adjunctive corticosteroid treatment is beneficial with
anti-PCPtherapyinpatientswithapartialpressureofoxygen(PaO
2
)less
than70mmHg,(A-a)DO
2
greaterthan35mmHg,oroxygensaturation
less than 90% on room air. Contraindications include suspected
tuberculosis or disseminated fungal infection. Treatment with methyl-
prednisolone(SoluMedrol)shouldbeginatthesametimeasanti-PCP
therapy.Thedosageis30mgIVq12hx5days,then30mgIVqdx5
days,then15mgqdx11daysORprednisone,40mgtwicedailyfor5
days,then40mgdailyfor5days,andthen20mgdailyuntilday21of
therapy.
VI. Prophylaxis
A.HIV-infected patients who have CD4 counts less than 200 cells/mcL
should receive prophylaxis against PCP. If CD4 count increases to
greater than 200 cells/mcL after receiving antiretroviral therapy, PCP
prophylaxiscanbesafelydiscontinued.
B.Trimethoprim-sulfamethoxazole(oncedailytothreetimesweekly)is
thepreferredregimenforPCPprophylaxis.
AntiretroviralTherapyandOpportunisticInfectionsinAIDS87
C.Dapsone(100mg dailyortwiceweekly)isaprophylacticregimenfor
patientswhocannottolerateTMP-SMX.
D.Aerosolizedpentamidine(NebuPent)300mgin6mLwaternebulized
over20minq4weeksisanotheralternative.
Antiretroviral Therapy and Opportunistic Infec-
tionsinAIDS
I. Antiretroviraltherapy
A. Acombinationofthreeagentsisrecommendedasinitialtherapy.The
preferredoptionsare2nucleosidesplus1proteaseinhibitoror1non-
nucleoside. Alternative options are 2 protease inhibitors plus 1
nucleosideor1non-nucleoside.Combinationsof1nucleoside,1non-
nucleoside,and1proteaseinhibitorarealsoeffective.
B. Nucleosideanalogs
1. Abacavir(Ziagen)300mgPObid[300mg].
2. Didanosine(Videx)200mgPObid[chewabletabs:25,50,100,150
mg];oralulcersdiscouragecommonusage.
3. Lamivudine(Epivir)150mgPObid[tab:150mg].
4. Stavudine(Zerit)40mgPObid[cap:15,20,30,40mg].
5. Zalcitabine(Hivid)0.75mgPOtid[tab:0.375,0.75mg].
6. Zidovudine(Retrovir,AZT)200mgPOtidor300mgPObid[cap:
100,300mg].
7. Zidovudine300mg/lamivudine150mg(Combivir)1tabPObid.
C. Proteaseinhibitors
1. Amprenavir(Agenerase)1200mgPObid[50,150mg]
2. Indinavir(Crixivan)800mgPOtid[cap:200,400mg].
3. Nelfinavir(Viracept)750mgPOtid[tab:250mg]
4. Ritonavir(Norvir)600mgPObid[cap:100mg].
5. Saquinavir(Invirase)600mgPOtid[cap:200mg].
D. Non-nucleosideanalogs
1. Delavirdine(Rescriptor)400mgPOtid[tab:100mg]
2. Efavirenz(Sustiva)600mgqhs[50,100,200mg]
3. Nevirapine(Viramune)200mgPObid[tab:200mg]
II. Oralcandidiasis
A. Fluconazole(Diflucan),acute:200mgPOx1,then100mgqdx5days
OR
B. Ketoconazole(Nizoral),acute:400mgpoqd1-2weeksoruntilresolved
OR
C. Clotrimazole (Mycelex) troches 10 mg dissolved slowly in mouth 5
times/d.
III. Candidaesophagitis
A. Fluconazole (Diflucan) 200 mg PO x 1, then 100 mg PO qd until
improved.
B. Ketoconazole(Nizoral)200mgpobid.
IV. PrimaryorrecurrentmucocutaneousHSV.Acyclovir(Zovirax),200-400
mgPO5timesadayfor10days,or5mg/kgIVq8h;orincasesofacyclovir
resistance,foscarnet40mg/kgIVq8hfor21days.
V. Herpessimplexencephalitis.Acyclovir10mg/kgIVq8hx10-21days.
VI.Herpesvaricellazoster
88AntiretroviralTherapyandOpportunisticInfectionsinAIDS
A. Acyclovir(Zovirax)10mg/kgIVover60minq8hOR
B. Valacyclovir(Valtrex)1000mgPOtidx7days[caplet:500mg].
VII. Cytomegalovirusinfections
A. Ganciclovir(Cytovene)5mg/kgIV(dilutein100mLD5Wover60min)
q12hx14-21days(concurrentusewithzidovudineincreaseshematolog-
icaltoxicity).
B. SuppressivetreatmentforCMV:Ganciclovir(Cytovene)5mg/kgIVqd,
or6mg/kgIV5times/wk,or1000mgorallytidwithfood.
VIII. Toxoplasmosis
A. Pyrimethamine 200 mg PO loading dose, then 50-75 mg qd plus
leucovorincalcium(folinicacid)10-20mgPOqdfor6-8weeksforacute
therapyAND
B. Sulfadiazine(1.0-1.5gmPOq6h)orclindamycin450mgPOqid/600-900
mgIVq6h.
C. Suppressivetreatmentfortoxoplasmosis
1. Pyrimethamine25-50mgPOqdwithorwithoutsulfadiazine0.5-1.0
gmPOq6h;andfolinicacid5-10mgPOqdOR
2. Pyrimethamine50mgPOqd;andclindamycin300mgPOq6h;and
folinicacid5-10mgPOqd.
IX. Cryptococcusneoformansmeningitis
A. AmphotericinBat0.7mg/kg/dIVfor14daysor untilclinicallystable,
followedbyfluconazole(Diflucan)400mgqdtocomplete10weeksof
therapy,followedbysuppressivetherapywithfluconazole(Diflucan)200
mgPOqdindefinitely.
B. AmphotericinBlipidcomplex(Abelcet)maybeused inplaceofnon-
liposomal amphotericin B if the patient is intolerant to non-liposomal
amphotericinB.Thedosageis5mg/kgIVq24h.
X. Activetuberculosis
A. Isoniazid (INH) 300 mg PO qd; and rifabutin 300 mg PO qd; and
pyrazinamide15-25mg/kgPOqd(500mgPObid-tid);andethambutol
15-25mg/kgPOqd(400mgPObid-tid).
B. All four drugs are continued for 2 months; isoniazid and rifabutin
(dependingonsusceptibilitytesting)arecontinuedforaperiodofatleast
9monthsandatleast6monthsafterthelastnegativecultures.
C. Pyridoxine(vitaminB6)50mgPOqd,concurrentwithINH.
XI. Disseminatedmycobacteriumaviumcomplex(MAC)
A. Azithromycin(Zithromax)500-1000mgPOqdorclarithromycin(Biaxin)
500mgPObid;AND
B. Ethambutol15-25mg/kgPOqd(400mgbid-tid)AND
C. Rifabutin300mg/d(two150mgtabletsqd).
D. ProphylaxisforMAC
1. Clarithromycin(Biaxin)500mgPObidOR
2. Rifabutin(Mycobutin)300mgPOqdor150mgPObid.
XII. Disseminatedcoccidioidomycosis
A. AmphotericinB(Fungizone)0.8mg/kgIVqdOR
B. AmphotericinBlipidcomplex(Abelcet)5mg/kgIVq24hOR
C. Fluconazole(Diflucan)400-800mgPOorIVqd.
XIII. Disseminatedhistoplasmosis
A. Amphotericin B (Fungizone) 0.5-0.8 mg/kg IV qd, until total dose 15
mg/kgOR
B. AmphotericinBlipidcomplex(Abelcet)5mg/kgIVq24hOR
C. Itraconazole(Sporanox)200mgPObid.
Sepsis89
D. Suppressivetreatmentforhistoplasmosis:Itraconazole(Sporanox)
200mgPObid.
Sepsis
SepsisisthemostcommoncauseofdeathinmedicalandsurgicalICUs.Mortal-
ityrangesfrom20-60%.Thesystemicinflammatoryresponsesyndrome(SIRS)
is an inflammatory response that is a manifestation of both sepsis and the
inflammatoryresponsethatresultsfromtraumaorburns.Thetermsepsisis
reservedforpatientswhohaveSIRSattributabletoinfection.
I. Pathophysiology
A. Althoughgram-negativebacteremiaiscommonlyfoundinpatientswith
sepsis, gram-positive infection may affect 30-40% of patients. Fungal,
viral and parasitic infections are usually encountered in
immunocompromisedpatients.
Definingsepsisandrelateddisorders
Term Definition
Systemicinflamma-
toryresponsesyn-
drome(SIRS)
Thesystemicinflammatoryresponsetoasevereclinical
insultmanifestedby$2ofthefollowingconditions:Tem-
perature>38Cor<36C,heartrate>90beats/min,respi-
ratoryrate>20breaths/minorPaCO
2
<32mmHg,white
bloodcellcount>12,000cells/mm
3
,<4000cells/mm
3
,or
>10%bandcells
Sepsis ThepresenceofSIRScausedbyaninfectiousprocess;
sepsisisconsideredsevereifhypotensionorsystemic
manifestationsofhypoperfusion(lacticacidosis,oliguria,
changeinmentalstatus)ispresent.
Septicshock Sepsis-inducedhypotensiondespiteadequatefluidresus-
citation,alongwiththepresenceofperfusionabnormali-
tiesthatmayinducelacticacidosis,oliguria,oranalter-
ationinmentalstatus.
Multipleorgandys-
functionsyndrome
(MODS)
Thepresenceofalteredorganfunctioninanacutelyill
patientsuchthathomeostasiscannotbemaintained
withoutintervention
B. Sourcesofbacteremialeadingtosepsisincludetheurinary,respiratory
andGItracts,andskinand softtissues(includingcathetersites).The
sourceofbacteremiaisunknownin30%ofpatients.
C. Escherichia coli is the most frequently encountered gram-negative
organism,followedbyKlebsiella,Enterobacter,Serratia,Pseudomonas,
Proteus, Providencia, and Bacteroides species. Up to 16% of sepsis
casesarepolymicrobic.
D. Gram-positive organisms, including Staphylococcus aureus and
Staphylococcusepidermidis,areassociatedwithcatheterorline-related
infections.
90Sepsis
II. Clinicalevaluation
A. Althoughfeveristhemostcommonsignofsepsis,normalbodytempera-
tures and hypothermia are common in the elderly. Tachypnea and/or
hyperventilationwithrespiratoryalkalosismayoccurbeforetheonsetof
feverorleukocytosis.Othercommonclinicalsignsofsystemicinflamma-
tionorimpairedorganperfusionincludealteredmentation,oliguria,and
tachycardia.
B. Intheearlystagesofsepsis,tachycardiaisassociatedwithincreased
cardiac output; peripheral vasodilation; and a warm, well-perfused
appearance.Asshockprogresses,vascularresistancecontinuestofall,
hypotension ensues and myocardial depression results in decreased
cardiacoutput.Duringthelaterstagesofsepticshock,vasoconstriction
andcoldextremitiesdevelop.
C. Laboratory findings. In the early stages of sepsis, arterial blood gas
measurements usually reveal respiratory alkalosis. As shock ensues,
metabolicacidosisbecomesapparent.Hypoxemiaiscommon.
ManifestationsofSepsis
Clinicalfeatures
Temperatureinstability
Tachypnea
Hyperventilation
Alteredmentalstatus
Oliguria
Tachycardia
Peripheralvasodilation
Laboratoryfindings
Respiratoryalkaloses
Hypoxemia
Increasedserumlactatelevels
Leukocytosisandincreasedneutrophil
concentration
Eosinopenia
Thrombocytopenia
Anemia
Proteinuria
Mildlyelevatedserumbilirubinlevels
D.Hemodynamics
1. The hallmark of early septic shock is a dramatic drop in systemic
vascularresistance,resultinginadecreaseinbloodpressure.
2. Cardiacoutputrisesinresponsetothefallinsystemicbloodpressure.
Thisisreferredtoasthehyperdynamicstateinsepsis.Shockresults
if the increase in cardiac output is insufficient to maintain blood
pressure. Diminished cardiac output may occur as systemic blood
pressurefalls.
III. Treatmentofsepsis
A.Resuscitation. Duringtheinitialresuscitationofahypotensivepatient
withsepsis,largevolumesofIVfluidshouldbegiven.Initialresuscitation
mayrequire4-6Lofcrystalloid.Fluidinfusionvolumesshouldbetitrated
toobtainapulmonarycapillarywedgepressureof10-20mmHg.Other
indicesoforganperfusionincludeoxygendelivery,serumlactatelevels,
arterialbloodpressure,andurinaryoutput.
B.Vasopressorandinotropictherapyisnecessaryifhypotensionpersists
despiteaggressivefluidresuscitation.
1. Dopamine is a first-line agent for sepsis-associated hypotension.
Begin with5:g/kg/minandtitratethedosagetothedesiredblood
pressureresponse,usuallyasystolicbloodpressureofgreaterthan
90mmHg.
Sepsis91
2. Norepinephrine or phenylephrine infusions may be used if
hypotension persists despite high dosages of dopamine (20
:g/kg/min), or if dopamine causes excessive tachycardia. These
agents have alpha-adrenergic effects, causing peripheral vaso-
constrictionandincreasedthemeanarterialpressure.
3. Dobutamine can be added to increase cardiac output through its
beta-adrenergicinotropiceffects.
4. Epinephrine has both alpha- and beta-adrenergic properties.
Epinephrinemaybeaddedifhypotensionpersistsdespitemaximum
dosesofdopamineandnorepinephrine.
C.ActivatedproteinCisavitaminK-dependentplasmaproteinwhichlimits
coagulationandaugmentsfibrinolysis.Inseveresepsis,activatedprotein
C(24mcg/kg/hrfor96hours)hasbeenshowntodecreasemortalityfrom
30.8to24.7%.Itshouldnotbeusedinpatientswiththrombocytopenia,
coagulopathy,recentsurgeryorrecenthemorrhagebecauseitincreases
theriskofbleeding.
VasoactiveandInotropicDrugs
Agent Dosage
Dopamine InotropicDose:5-10mcg/kg/min
VasoconstrictingDose:10-20mcg/kg/min
Dobutamine Inotropic:5-10mcg/kg/min
Vasodilator:15-20mcg/kg/min
Norepinephrine Vasoconstrictingdose:2-8mcg/min
Phenylephrine Vasoconstrictingdose:20-200mcg/min
Epinephrine Vasoconstrictingdose:1-8mcg/min
A.Diagnosisandmanagementinfection
1. Initial treatment of life-threatening sepsis usually consists of a
third-generationcephalosporin(ceftazidime,cefotaxime,ceftizoxime),
piperacillin/tazobactam,orimipenem.Anaminoglycoside(gentamicin,
tobramycin,oramikacin)shouldalsobeincluded.Antipseudomonal
coverageisimportantforhospital- orinstitutional-acquiredinfections.
Appropriate choices include an antipseudomonal penicillin,
cephalosporin,oranaminoglycoside.
2. Methicillin-resistant staphylococci. If line sepsis or an infected
implanteddeviceisapossibility,vancomycinshouldbeaddedtothe
regimentocoverformethicillin-resistantStaphaureusandmethicillin-
resistantStaphepidermidis.
3. Intra-abdominalorpelvicinfectionsarelikelytoinvolveanaerobes;
therefore, treatment should include either piperacillin/tazobactam
(Zosyn),imipenem(Primaxin),ormeropenem(Merrem).Alternatively,
metronidazolewithanaminoglycosideandampicillinmaybeinitiated.
4. Biliarytractinfections.Whenthesourceofbacteremiaisthebiliary
tract,piperacillin/tazobactam(Zosyn)orcefoperazone(Cefobid)may
beused.Anaminoglycosideplusclindamycinisanalternative.
92Sepsis
Dosagesofantibioticsusedinsepsis
Agent Dosage
Cefotaxime(Claforan) 2gmq4-6h
Ceftizoxime(Cefizox) 2gmIVq8h
Cefoxitin(Mefoxin) 2gmq6h
Cefotetan(Cefotan) 2gmIVq12h
Ceftazidime(Fortaz) 2gIVq8h
Ticarcillin/clavulanate(Timentin) 3.1gmIVq4-6h(200-300mg/kg/d)
Ampicillin/sulbactam(Unasyn) 3.0gmIVq6h
Piperacillin/tazobactam(Zosyn) 3.375-4.5gmIVq6h
Piperacillin,ticarcillin,mezlocillin 3gmIVq4-6h
Meropenem(Merrem) 1gmIVq8h
Imipenem/cilastatin(Primaxin) 1.0gmIVq6h
Gentamicinortobramycin 2mg/kgIVloadingdose,then1.7
mg/kgIVq8h
Amikacin(Amikin) 7.5mg/kgIVloadingdose,then5
mg/kgIVq8h
Vancomycin 1gmIVq12h
Metronidazole(Flagyl) 500mgIVq6-8h
Linezolid(Zyvox) 600mgIV/POq12h
Quinupristin/dalfopristin(Synercid) 7.5mg/kgIVq8h
5. Vancomycin-resistantenterococcus(VRE):Anincreasingnumber
ofenterococcalstrainsareresistanttoampicillinandgentamicin.The
incidence of vancomycin-resistant enterococcus (VRE) is rapidly
increasing.
a.Linezolid (Zyvox) is an oral or parenteral agent active against
vancomycin-resistant enterococci, including E. faecium and E.
faecalis. Linezolid is also active against methicillin-resistant
staphylococcusaureus.
b.Quinupristin/dalfopristin(Synercid)isaparenteralagentactive
againststrainsofvancomycin-resistantenterococcusfaecium,but
Peritonitis93
notenterococcusfaecalis.MoststrainsofVREareenterococcus
faecium.
Peritonitis
I. AcutePeritonitis
A. Acuteperitonitisisinflammationoftheperitoneumorperitonealfluidfrom
bacteria or intestinal contents in the peritoneal cavity. Secondary
peritonitisresultsfromperforationofaviscuscausedbyacuteappendici-
tisordiverticulitis,perforationofanulcer,ortrauma.Primaryperitonitis
refers to peritonitis arising without a recognizable preceding cause.
Tertiaryperitonitisconsistsofpersistentintra-abdominalsepsiswithout
adiscretefocusofinfection,usuallyoccurringaftersurgicaltreatmentof
peritonitis.
B. Clinicalfeatures
1. Acuteperitonitispresentswithabdominalpain,abdominaltenderness,
andtheabsenceofbowelsounds.Severe,sudden-onsetabdominal
painsuggestsarupturedviscus.Signsofperitonealirritationinclude
abdominaltenderness,reboundtenderness,andabdominalrigidity.
2. In severe cases, fever, hypotension, tachycardia, and acidosis may
occur.Spontaneousbacterialperitonitisarisingfromasciteswilloften
presentwithonlysubtlesigns.
C. Diagnosis
1. Plainabdominalradiographsandachestx-raymaydetectfreeair
in the abdominal cavity caused by a perforated viscus. CT and/or
ultrasonographycanidentifythepresenceoffreefluidoranabscess.
2. Paracentesis
a. Tube1-Cellcountanddifferential(1-2mL,EDTApurpletoptube)
b. Tube2- Gramstainofsediment;C&S,AFB,fungalC&S(3-4mL);
inject 10-20 mL into anaerobic and aerobic culture bottle at the
bedside.
c. Tube 3 - Glucose, protein, albumin, LDH, triglyceride, specific
gravity, amylase, (2-3 mL, red top tube). Serum/fluid albumin
gradientshouldbedetermined.
d. Syringe-pH(3mL).
D. Treatmentofacuteperitonitis
1. Resuscitationwithintravenousfluidsandcorrectionofmetabolicand
electrolytedisturbancesaretheinitialsteps.Laparotomyisacorner-
stoneoftherapyforsecondaryortertiaryacuteperitonitis.
2. Broad-spectrumsystemicantibioticsarecriticaltocoverbowelflora,
includinganaerobicspecies.
3. Mildtomoderateinfection(community-acquired)
a. Cefotetan(Cefotan)1-2gmIVq12hOR
b. Ampicillin/sulbactam(Unasyn)3.0gmIVq6h
c. Ticarcillin/clavulanate(Timentin)3.1gmIVq6h
4. Severeinfection(hospital-acquired)
a. Cefepime(Maxipime)2gmIVq12handmetronidazole(Flagyl)500
mgIVq6hOR
b. Piperacillin/tazobactam(Zosyn)3.375gmIVq6hOR
c. Imipenem/cilastatin(Primaxin)1gIVq6hOR
94Peritonitis
d. Ciprofloxacin(Cipro)400mgIVq12handclindamycin600mgIV
q8hOR
e. Gentamicinortobramycin100-120mg(1.5mg/kg);then80mgIV
q8h(3-5mg/kg/d)andmetronidazole(Flagyl)500mgIVq6h.
II. Spontaneousbacterialperitonitis
A. SBP,whichhasnoobviousprecipitatingcause,occursalmostexclusively
incirrhoticpatients
B. Diagnosis
1. Spontaneous bacterial peritonitis is diagnosed by paracentesis in
whichtheasciticfluidisfoundtohave250ormorepolymorphonuclear
(PMN)cellspercubicmillimeter.
C. Therapy
1. AntibioticsarethecornerstoneofmanagingSBP,andlaparotomyhas
noplaceintherapyforSBP,unlessperforationispresent.Threeto5
days of intravenous treatment with broad-spectrum antibiotics is
usually adequate, at which time efficacy can be determined by
estimatingtheasciticfluidPMNcellcount.
2. Option1:
a. Cefotaxime(Claforan)2gmIVq4-6h
3. Option2:
a. Ticarcillin/clavulanate(Timentin)3.1gmIVq6hOR
b. Piperacillin/tazobactam(Zosyn)3.375gmIVq6hor4.5gmIVq8h.
4. Option3ifextended-spectrumbeta-lactamase(ESBL):
a. Imipenem/cilastatin(Primaxin)1.0gmIVq6h.OR
b. Ciprofloxacin(Cipro)400mgIVq12hOR
c. Levofloxacin(Levaquin)500mgIVq24h.
References
DrugsforHIVInfection.TheMedicalletter2000;42:1-6.
Prefacetothe1997USPHS/IDSAGuidelinesforthePreventionofOpportunisticInfections
inPersonsInfectedwithHIV.
1997 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with
UnexplainedFever.ClinicalInfectiousDiseases1997;25:551-73
HughesW.T.OpportunisticInfectionsinAIDSPatients.OpportunisticInfections95:81-93,
1994
LaneHCLaughonB.E.FalloonJ.,et.al.RecentAdvancesintheManagementofAIDS-
relatedOpportunisticInfections. Ann.Intern.Med.120:945-955,1994.
Tunkel A.R, Wispelway B, Scheld W.N: Bacterial meningitis; Recent advances in
pathophysiologyandtreatment.AnnIntMed112:610,1990.
PachonJ,etal:Severecommunityacquiredpneumonia.AmRevRespirDis142:36973,
1990
Whittman,DH.ManagementofSecondaryPeritonitis.AnnalsofSurgery.1996;224(1):10-
18.
Bernard,GR,etal.Efficacy and SafetyofRecombinant Human Activated Protein C for
SevereSepsis.NEJM.2001;Vol334,No10:699-709.
UpperGastrointestinalBleeding95
Gastroenterology
MichaelKrutzik,MD
H.L.Daneschvar,MD
S.E.Wilson,MD
RohamT.Zamanian,MD
UpperGastrointestinalBleeding
I. Clinicalevaluation
A. Initial evaluation of upper GI bleeding should estimate the severity,
duration,location,andcauseofbleeding.Ahistoryofbleedingoccurring
afterforcefulvomitingsuggestsMallory-WeissSyndrome.
B. Abdominal pain, melena, hematochezia (bright red blood per rectum),
historyofpepticulcer,cirrhosis orpriorbleedingepisodesmay bepresent.
C. Precipitating factors. Use of aspirin, nonsteroidal anti-inflammatory
drugs,alcohol,oranticoagulantsshouldbesought.
II. Physicalexamination
A. General: Pallor and shallow, rapid respirations may be present; tachy-
cardiaindicatesa10%bloodvolumeloss.Posturalhypotension(increase
inpulseof20andasystolicbloodpressurefallof10-15mmHg),indicates
a20-30%loss.
B. Skin:Delayedcapillaryrefillandstigmataofliverdisease(jaundice,spider
angiomas,parotidglandhypertrophy)shouldbesought.
C. Abdomen: Scars, tenderness, masses, hepatomegaly, and dilated
abdominalveinsshouldbeevaluated.Stoolgrossoroccultbloodshould
bechecked.
III. Laboratory evaluation: CBC, SMA 12, liver function tests, amylase,
INR/PTT,typeandcrossforpRBC,FFP,EKG.
IV. Differential diagnosis of upper bleeding: Peptic ulcer, gastritis, esop-
hageal varices, Mallory-Weiss tear, esophagitis, swallowed blood from
epistaxis,malignancy(esophageal,gastric),angiodysplasias,aorto-enteric
fistula,hematobilia.
V. Managementofuppergastrointestinalbleeding
A. If the bleeding appears to have stopped or has significantly slowed,
medicaltherapywithH2blockersandsalinelavageisusuallyallthatis
required.
B. Two 14-to16-gaugeIVlinesshouldbeplaced.Normalsalinesolution
shouldbeinfuseduntilbloodisready,thentransfuse2-6unitsofpRBCs
asfastaspossible.Anestimateofbloodtransfusionrequirementshould
bebasedonthebloodlossrate and vitalsigns(typically2-6unitsare
needed).
C. Alargeborenasogastrictubeshouldbeplaced,followedbylavagewith
2Lofroomtemperaturetapwater.Thetubeshouldthenbeconnected
tolowintermittentsuction,andthelavageshouldberepeatedhourly.The
NGtubemayberemovedwhenbleedingisnolongeractive.
D. Oxygenisadministeredbynasalcannula,guidedbypulseoximetry.Urine
outputshouldbemonitored.
E. Serialhematocritsshouldbecheckedandmaintainedgreaterthan30%.
96Varicealbleeding
F. Coagulopathy should be assessed and corrected with fresh frozen
plasma,vitaminK,cryoprecipitate,andplatelets.
G. Definitive diagnosis requires upper endoscopy, at which time
electrocoagulation,banding,and/orlocalinjectionofvasoconstrictorsat
bleedingsitesmaybecompleted.
H. Surgicalconsultationshouldberequestedinunstablepatientsorpatients
whorequiremorethan6unitsofpRBCs.
VI.Mallory-Weisssyndrome
A. This disorder is defined as a mucosal tear at the gastroesophageal
junctionfollowingforcefulretchingandvomiting.
B. Treatment is supportive, and the majority of patients stop bleeding
spontaneously.Endoscopiccoagulationoroperativesuturingmayrarely
benecessary.
VII. Acutemedicaltreatmentofpepticulcerdisease
A. Ranitidine(Zantac)50mgIVbolus,thencontinuousinfusionat6.25-12.5
mg/h[150-300mgin250mLD5Wover24h(11cc/h)],or50mgIVq6-8h
OR
B. Cimetidine(Tagamet)300mgIVbolus,thencontinuousinfusionat37.5-
50mg/h(900mgin250mLD5Wover24h),or300mgIVq6-8hOR
C. Famotidine(Pepcid)20mgIVq12h.
VaricealBleeding
Hemorrhagefromesophagealandgastricvaricesusuallyoccursasacomplica-
tionofchronicliverdisease.
I. Clinicalevaluation
A. Varicealbleedingshouldbeconsideredinanypatientwhopresentswith
significantuppergastrointestinalbleeding.Signsofcirrhosismayinclude
spiderangiomas,palmarerythema,leukonychia,clubbing,parotidenlarge-
ment,andDupuytren'scontracture.Jaundice,lowerextremityedemaand
ascitesareindicativeofdecompensatedliverdisease.
B.The severity of the bleeding episode can be assessed on the basis of
orthostaticchanges(eg,restingtachycardia,posturalhypotension),which
indicatesone-thirdormoreofbloodvolumeloss.
C.If thepatient'ssensoriumisalteredbecauseofhepaticencephalopathy,the
riskofaspirationmandatesendotrachealintubation.Placementofalarge-
calibernasogastrictube(22For24F)permitslavageforremovalofblood
andclotsinpreparationforendoscopy.
D.Nasogastriclavageshouldbeperformedwithtapwater,becausesaline
maycontributetoretentionofsodiumandwater.
II. Resuscitation
A. Bloodshouldbereplacedassoonaspossible.Whilebloodfortransfusion
isbeingmadeavailable,intravascularvolumeshouldbereplenishedwith
normalsalinesolution.
B.Once euvolemia is established, the intravenous infusion should be
changedtosolutionswithalowersodiumcontent(5%dextrosewithor
normalsaline).
C.Fresh frozen plasma is administered to patients who have been given
massivetransfusions.Each3unitsofPRBCshouldbeaccompaniedby
CaCL
2
1gmIVover30min.
VaricealBleeding97
D.Bloodshouldbetransfusedtomaintainahematocritofatleast30%.Serial
hematocritestimationsshouldbeobtainedduringcontinuedbleeding.
III. Treatmentofvaricealhemorrhage
A. Pharmacologicagents
1. Octreotide (Sandostatin) 50 mcg IV over 5-10 min, followed by 50
mcg/h for 48 hours (1200 mcg in 250 mL D5W). Octreotide is a
somatostatinanalog,whichisbeneficialincontrollinghemorrhage.
2. Vasopressin (Pitressin), a posterior pituitary hormone, causes
splanchnicarteriolarvasoconstrictionandreductioninportalpressure.
a. Dosageis20unitsIVover20-30min,then0.2-0.4units/minute(100
Uin250mLD5W).
b. ConcomitantuseofIVnitroglycerinpaste(1inchq6h)mitigatesthe
vasoconstrictor effects of vasopressin on the myocardial and
splanchniccirculations.
B.Tamponadedevices
1. Bleedingfromvaricesmay temporarilybereducedwithtamponadebal-
loon tubes. However, the benefit is temporary, and prolonged
tamponade causes severe esophageal ulceration and has a high
rebleeding rate. The Linton-Nachlas tube has a gastric balloon and
severalportsintheesophagealcomponent.Thetubeiskeptinplace
for6-12hourswhilepreparationsforendoscopicorradiologictreatment
arebeingmade.
C.Endoscopicmanagementofbleedingvarices
1. Endoscopic sclerotherapy involves injection of a sclerosant into
varices. The success of the treatment is enhanced by a second
sclerotherapytreatment.
2. Endoscopicvaricealligationinvolvesplacementoftinyrubberbands
on varices during endoscopy. Ligation is associated with fewer
complicationsthansclerotherapy,butbothhavecomparableefficacy.
D.Surgery
1. Portal-systemicshuntsurgeryisthemostdefinitivetherapyforbleeding
varices. However, the procedures have a 30-40% rate of hepatic
encephalopathy, and there is only a slight survival advantage over
medicaltreatment.
2. Shuntsthatpreserveportalbloodflowarepreferred,suchasthedistal
splenorenalandthesmall-diameterportacavalH-graftshunts.
E. Transjugularintrahepaticportacavalshunt(TIPS)
1. Under fluoroscopy, a needle is advanced into the liver through the
internaljugularandhepaticveins,andinsertedintoalargebranchof
theportalvein.Aballoonisthenusedtoenlargethetracktopermitthe
placementofastent.
2. Encephalopathy occurs in about 35% of patients, and there is a
significantriskofshuntthrombosisorstenosis.
IV. Approachtotreatmentofvaricealhemorrhage
A. Patientsinitiallyshouldbegivenoctreotide(Sandostatin)orvasopressin
infusionplusnitroglycerinwhileawaitingendoscopictreatment.
B.Ifvaricesarelarge,endoscopicligationispreferred.Ifthereisactivebleed-
ingfromaspurtingvarix,sclerotherapyisbest.
C.Failureofendoscopictherapywarrantstheuseofaportal-systemicshunt.
Livertransplantationshouldbeconsideredinpoor-riskpatientsandwhen
othertherapiesfail.
98LowerGastrointestinalBleeding
LowerGastrointestinalBleeding
H.L.Daneschvar,MD
S.E.Wilson,MD
The spontaneous remission rates for lower gastrointestinal bleeding is 80
percent.Nosourceofbleedingcanbeidentifiedin12percentofpatients,and
bleedingisrecurrentin25percent.Bleedinghasusuallyceasedbythetimethe
patientpresentstotheemergencyroom.
I. Clinicalevaluation
A. Theseverityofbloodlossandhemodynamicstatusshouldbeassessed
immediately.Initialmanagementconsistsofresuscitationwithcrystalloid
solutions(lactatedRingerssolution)andbloodproductsifnecessary.
B.Thedurationandquantityofbleedingshouldbeassessed;however,the
durationofbleedingisoftenunderestimated.
C.Risk factors that may have contributed to the bleeding include and
nonsteroidalanti-inflammatorydrugs,anticoagulants,colonicdiverticulitis,
renalfailure,coagulopathy,colonicpolyps,andhemorrhoids.Patientsmay
have a prior history of hemorrhoids, diverticulosis, inflammatory bowel
disease,pepticulcer,gastritis,cirrhosis,oresophagealvarices.
D.Hematochezia.Brightredormaroonoutputperrectumsuggestsalower
GIsource;however12to20%ofpatientswithanupperGIbleedmayhave
hematocheziaasaresultofrapidbloodloss.
E. Melena.Sticky,black,foul-smellingstoolssuggestasourceproximaltothe
ligamentofTreitz,butMelenacanalsoresultfrombleedinginthesmall
intestineorproximalcolon.
F. Change in stool caliber, anorexia, weight loss and malaise are
suggestiveofmalignancy.
G. Clinicalfindings
1. Abdominalpainmayresultfromischemicbowel,inflammatorybowel
disease,orarupturedaneurysm.
2. Painless massive bleeding suggests vascular bleeding from
diverticula,angiodysplasia,orhemorrhoids.
3. Bloodydiarrheasuggests inflammatoryboweldiseaseoraninfectious
origin.
4. Bleedingwithrectalpainisseenwithanalfissures,hemorrhoids,and
rectalulcers.
5. Chronicconstipationsuggestshemorrhoidalbleeding.Newonsetof
constipationorthinstoolssuggestsaleftsidedcolonicmalignancy.
6. Bloodonthetoiletpaperordrippingintothetoiletwatersuggestsa
perianalsourceofbleeding,suchashemorrhoidsorananalfissure.
7. Bloodcoatingtheoutsideofstoolssuggestsalesionintheanalcanal.
8. Bloodstreakingormixedinwiththestoolmayresultsfrompolypsor
amalignancyinthedescendingcolon.
9. Marooncoloredstoolsoftenindicatesmallbowelandproximalcolon
bleeding.
II. Physicalexamination
A. Posturalhypotensionindicatesa20%bloodvolumeloss,whereas,overt
signs of shock (pallor, hypotension, tachycardia) indicates a 30 to 40
percentbloodloss.
LowerGastrointestinalBleeding99
B.The skin may be cool and pale with delayed refill if bleeding has been
significant.
C.Stigmata of liver disease, including jaundice, caput medusae,
gynecomastiaandpalmarerythema,shouldbesoughtbecausepatients
withthesefindingsfrequentlyhaveGIbleeding.
III. DifferentialdiagnosisoflowerGIbleeding
A. Angiodysplasiaanddiverticulardiseaseoftherightcolonaccountsforthe
vastmajorityofepisodesofacutelowerGIbleeding.MostacutelowerGI
bleedingoriginatesfromthecolonhowever15to20percentofepisodes
arisefromthesmallintestineandtheupperGItract.
B.Elderlypatients.Diverticulosisandangiodysplasiaarethemostcommon
causesoflowerGIbleeding.
C.Younger patients. Hemorrhoids, anal fissures and inflammatory bowel
diseasearemostcommoncausesoflowerGIbleeding.
IV. Diagnosisandmanagementoflowergastrointestinalbleeding
A. Rapidclinicalevaluationandresuscitationshouldprecedediagnostic
studies. Intravenous fluids (1 to 2 liters) should be infused over 10- 20
minutestorestoreintravascularvolume,andbloodshouldbetransfused
if there is rapid ongoing blood loss or if hypotension or tachycardia are
present.Coagulopathyiscorrectedwithfreshfrozenplasma,platelets,and
cryoprecipitate.
B.Whensmallamountsofbrightredbloodarepassedperrectum,thenlower
GItractcanbeassumedtobethesource.Inpatientswithlargevolume
maroonstools,nasogastric tubeaspirationshouldbeperformedtoexclude
massiveuppergastrointestinalhemorrhage.
C.If the nasogastric aspirate contains no blood then anoscopy and
sigmoidoscopy should be performed to determine weather a colonic
mucosalabnormality(ischemicorinfectiouscolitis)orhemorrhoidsmight
bethecauseofbleeding.
D.Colonoscopy in a patient with massive lower GI bleeding is often
nondiagnostic, but it can detect ulcerative colitis, antibiotic-associated
colitis,orischemiccolon.
E. Polyethyleneglycol-electrolytesolution(ColyteorGoLytely)shouldbe
administered by means of a nasogastric tube (Four liters of solution is
given over a 2-3 hour period), allowing for diagnostic and therapeutic
colonoscopy.
V. Definitivemanagementoflowergastrointestinalbleeding
A. Colonoscopy
1. Colonoscopyistheprocedureofchoicefordiagnosingcoloniccauses
ofGIbleeding.Itshouldbeperformedafteradequatepreparationofthe
bowel. If the bowel cannot be adequately prepared because of
persistent,acutebleeding,ableedingscanorangiographyisprefera-
ble.
2. Endoscopymaybetherapeuticforangiodysplasticlesions,orpolyps,
whichcanbecoagulated.
3. If colonoscopy fails to reveal the source of the bleeding, the patient
should be observed because, in 80% of cases, bleeding ceases
spontaneously.
B.Radionuclidescanorbleedingscan.Technetium- labeled(tagged)red
blood cell bleeding scans can detect bleeding sites when bleeding is
intermittent.Localizationmaynotheapreciseenoughtoallowsegmental
colonresection.
100LowerGastrointestinalBleeding
C.Angiography.Selectivemesentericangiographydetectsarterialbleeding
thatoccurs atratesof0.5mL/perminuteorfaster.Diverticularbleeding
causes pooling of contrast medium within a diverticulum. Bleeding
angiodysplastic lesions appear as abnormal vasculature. When active
bleeding is seen with diverticular disease or angiodysplasia, selective
arterialinfusionofvasopressinmaybeeffective.
D.Surgery
1. Ifbleedingcontinuesandnosourcecanbefound,surgicalintervention
isusuallywarranted.
2. Surgical resection may be indicated for patients with recurrent
diverticularbleeding,orforpatientswhohavehadpersistentbleeding
from colonic angiodysplasia and have required blood transfusions.
Treatmentoflowergastrointestinalbleedinginvolvesresectionofthe
involvedsegments.
VI. Angiodysplasia
A. Angiodysplastic lesions are small vascular tufts that are formed by
capillaries,veinsandvenules,appearingoncolonoscopyasreddotsorto
2 to 10 mm spider-like lesions. Angiodysplastic lesions developed
secondarytochroniccolonicdistention,andtheyhaveaprevalenceof25
percentinelderlypatients.
B.Themostcommonsiteofbleedingis therightcolon.Mostpatientswith
angiodysplasiahaverecurrentminorbleeding;however,massivebleeding
mayoccur.
VII. Diverticulardisease
A. Diverticulardiseaseisthemostcommoncauseofacutelowergastrointes-
tinalbleeding.Approximately60-80%ofbleedingdiverticulaarelocatedin
therightcolon.About90%ofalldiverticulaarefoundintheleftcolon.
B.Diverticular bleedingtendstobemassive,butitstopsspontaneouslyin
80%ofpatients.Therateofrebleedingis25%.
VIII. Colonpolypsandcoloncancers
A. ColonicpolypsandcoloniccancersrarelycausesignificantacutelowerGI
bleeding.Leftsidedandrectalneoplasmsaremorelikelytocausegross
bleeding than right-sided lesions. Right-sided lesions are more likely to
causeanemiaandoccultbleeding.
B.Diagnosis and treatment of colonic polyps consists of colonoscopic
excisionorsurgicalresection.
IX. Inflammatoryboweldisease
A. Ulcerativecolitiscanoccasionallycauseseveregastrointestinalbleeding
associatedwiththeabdominalpainanddiarrhea.
B.Colonoscopy and biopsy is diagnostic, and therapy consists of medical
treatmentoftheunderlyingdisease.Resectionisrequiredoccasionally.
X. Ischemiccolitis
A. Ischemiccolitisis seeninelderlypatientswithknownvasculardisease.
The abdomen pain may be postprandial and associated with bloody
diarrheaorrectalbleeding.Severebloodlossisunusualbutcanoccur.
B.Abdominal films may reveal "thumb-printing" caused by submucosal
edema.Colonoscopyrevealsawell-demarcatedareaofhyperemia,edema
andmucosalulcerations.Thesplenicflexureanddescendingcolonarethe
most common sites. Most episodes resolve spontaneously, however,
vascularbypassorresectionmayberequired.
XI. Hemorrhoids
AcutePancreatitis101
A. Hemorrhoidsrarelycausemassiveacutebloodloss.Inpatientswithportal
hypertension,rectalvaricesshouldbeconsidered.
B.Diagnosisisbyanoscopyandsigmoidoscopy.Treatmentconsistsofhigh-
fiberdiets,stoolsofteners,and/orhemorrhoidectomy.
AcutePancreatitis
BlandingU.Jones,MDandRussellA.Williams,MD
Theincidenceofacutepancreatitisrangesfrom54to238episodesper1million
peryear.Patientswithmildpancreatitisrespondwelltoconservativetherapy,but
those with severe pancreatitis may have a progressively downhill course to
respiratoryfailure,sepsis,anddeath(lessthan10%).
I. Etiology
A. Alcohol-inducedpancreatitis.Consumptionoflargequantitiesofalcohol
maycauseacutepancreatitis.
B.Cholelithiasis.Commonbileductorpancreaticductobstructionbyastone
may cause acute pancreatitis. (90% of all cases of pancreatitis occur
secondarytoalcoholconsumptionorcholelithiasis).
C. Idiopathicpancreatitis.Thecauseofpancreatitiscannotbedetermined
in10percentofpatients.
D. Hypertriglyceridemia.Elevationofserumtriglycerides(>l,000mg/dL)has
beenlinkedwithacutepancreatitis.
E. Pancreaticductdisruption.Inyoungerpatients,amalformationofthe
pancreaticducts(eg,pancreaticdivisum)withsubsequentobstructionis
often the cause of pancreatitis. In older patients without an apparent
underlyingetiology,cancerouslesionsoftheampullaofVater,pancreasor
duodenummustberuledoutaspossiblecausesofobstructivepancreatitis.
F. Iatrogenicpancreatitis.Radiocontraststudiesofthehepatobiliarysystem
(eg, cholangiogram, ERCP) can cause acute pancreatitis in 2-3% of
patientsundergoingstudies.
G. Trauma.Bluntorpenetratingtraumaofanykindtotheperi-pancreaticor
peri-hepatic regions may induce acute pancreatitis. Extensive surgical
manipulationcanalsoinducepancreatitisduringlaparotomy.
CausesofAcutePancreatitis
Alcoholism
Cholelithiasis
Drugs
Hypertriglyceridemia
Idiopathiccauses
Infections
Microlithiasis
Pancreasdivisum
Trauma
102AcutePancreatitis
MedicationsAssociatedwithAcutePancreatitis
Asparaginase(Elspar)
Azathioprine(Imuran)
Didanosine(Videx)
Estrogens
Ethacrynicacid(Edecrin)
Furosemide(Lasix)
Mercaptopurine(Purinethol)
Pentamidine
Sulfonamides
Tetracyclines
Thiazidediuretics
Valproicacid(Depakote)
II. Pathophysiology.Acutepancreatitis resultswhenaninitiatingeventcauses
the extrusion of zymogen granules, from pancreatic acinar cells, into the
interstitium of the pancreas. Zymogen particles cause the activation of
trypsinogenintotrypsin.Trypsincausesauto-digestionofpancreatictissues.
III. Clinicalpresentation
A. Signsandsymptoms.Pancreatitisusuallypresentswithmid-epigastric
painthatradiatestotheback,associatedwithnauseaandvomiting.The
painissuddeninonset,progressivelyincreasesinintensity,andbecomes
constant.Theseverityofpainoftencausesthepatienttomovecontinu-
ouslyinsearchofamorecomfortableposition.
B. Physicalexamination
1. Patients with acute pancreatitis often appear very ill. Findings that
suggestseverepancreatitisincludehypotensionandtachypneawith
decreasedbasilarbreathsounds.Flankecchymoses(GreyTuner's
Sign)orpedumbilical ecchymoses(Cullen'ssign)maybeindicative
ofhemorrhagicpancreatitis.
2. Abdominal distensionandtendernessintheepigastriumarecommon.
Feverandtachycardiaareoftenpresent.Guarding,reboundtender-
ness, and hypoactive or absent bowel sounds indicate peritoneal
irritation.Deeppalpationofabdominal organsshouldbeavoidedinthe
settingofsuspectedpancreatitis.
IV. Laboratorytesting
A. Leukocytosis.AnelevatedWBCwithaleftshiftandelevatedhematocrit
(indicatinghemoconcentration)andhyperglycemiaarecommon.Pre-renal
azotemia may result from dehydration. Hypoalbuminemia, hyper-
triglyceridemia,hypocalcemia,hyperbilirubinemia,andmildelevationsof
transaminasesandalkalinephosphatasearecommon.
B. Elevatedamylase.Anelevatedamylaseleveloftenconfirmstheclinical
diagnosisofpancreatitis.
C. Elevatedlipase.Lipasemeasurementsaremorespecificforpancreatitis
thanamylaselevels,butlesssensitive.Hyperlipasemiamayalsooccur
inpatientswithrenalfailure,perforatedulcerdisease,bowelinfarctionand
bowelobstruction.
D. AbdominalRadiographsmayrevealnon-specificfindingsofpancreatitis,
suchas"sentinelloops"(dilatedloopsofsmallbowelinthevicinityofthe
pancreas),ileusand,pancreaticcalcifications.
E. Ultrasonographydemonstratestheentirepancreasinonly20percentof
patients with acute pancreatitis. Its greatest utility is in evaluation of
patientswithpossiblegallstonedisease.
F. Helicalhighresolutioncomputedtomographyistheimagingmodality
ofchoiceinacutepancreatitis.CTfindingswillbenormalin14-29%of
AcutePancreatitis103
patients with mild pancreatitis. Pancreatic necrosis, pseudocysts and
abscessesarereadilydetectedbyCT.
SelectedConditionsOtherThanPancreatitisAssociatedwithAmy-
laseElevation
Carcinomaofthepancreas
Commonbileductobstruction
Post-ERCP
Mesentericinfarction
Pancreatictrauma
Perforatedviscus
Renalfailure
Acutealcoholism
Diabeticketoacidosis
Lungcancer
Ovarianneoplasm
Renalfailure
Rupturedectopicpregnancy
Salivaryglandinfection
Macroamylasemia
V. Prognosis. Ranson's criteria is used to determine prognosis in acute
pancreatitis.Patientswithtwoorfewerriskfactorshaveamortalityrateof
lessthan1percent,thosewiththreeorfourrisk-factorsamortalityrateof16
percent,fiveorsixriskfactors,amortalityrateof40percent,andsevenor
eightriskfactors,amortalityrateapproaching100percent.
Ranson'sCriteriaforAcutePancreatitis
Atadmission Duringinitial48hours
1.Age>55years
2.WBC>16,000/mm
3
3.Bloodglucose>200mg/dL
4.SerumLDH>350IU/L
5.AST>250U/L
1.Hematocritdrop>10%
2.BUNrise>5mg/dL
3.ArterialpO
2
<60mmHg
4.Basedeficit>4mEq/L
5.Serumcalcium<8.0mg/dL
6.Estimatedfluidsequestration>6L
VI.Treatmentofpancreatitis
A.Expectantmanagement.Mostcasesofacutepancreatitiswillimprove
within three to seven days. Management consists of prevention of
complicationsofseverepancreatitis.
B.NPO and bowel rest. Patients should take nothing by mouth. Total
parenteralnutritionshouldbeinstitutedforthosepatientsfastingformore
thanfivedays.Anasogastrictubeiswarrantedifvomitingorileus.
C.IVfluidresuscitation.Vigorousintravenoushydrationisnecessary.A
decreaseinurineoutputtolessthan30mLperhourisanindicationof
inadequatefluidreplacement.
D.Pain control. Morphine is discouraged because it may cause Oddi's
sphincter spasm, which may exacerbate the pancreatitis. Meperidine
(Demerol),25-100mgIV/IMq4-6h,isfavored.Ketorolac(Toradol),60mg
IM/IV,then15-30mgIM/IVq6h,isalsoused.
E. Antibiotics.Routineuseofantibioticsisnotrecommendedinmostcases
ofacutepancreatitis.Incasesofinfectiouspancreatitis,treatmentwith
cefoxitin(1-2gIVq6h),cefotetan(1-2gIVq12h),imipenem(1.0gmIV
q6h),orampicillin/sulbactam(1.5-3.0gIVq6h)maybeappropriate.
104HepaticEncephalopathy
F. Alcohol withdrawal prophylaxis. Alcoholics may require alcohol
withdrawal prophylaxis with lorazepam (Ativan) 1-2mg IM/IV q4-6h as
neededx3days,thiamine100mgIM/IVqdx3days,folicacid1mgIM/IV
qdx3days,multivitaminqd.
G. Octreotide.Somatostatinisalsoapotentinhibitorofpancreaticexocrine
secretion. Octreotide is a somatostatin analogue, which has been
effectiveinreducingmortalityfrombile-inducedpancreatitis.Clinicaltrials,
however,havefailedtodocumentasignificantreductioninmortality
H.Bloodsugarmonitoringandinsulinadministration.Serumglucose
levelsshouldbemonitored.
VII. Complications
A.Chronicpancreatitis
B.Severehemorrhagicpancreatitis
C.Pancreaticpseudocysts
D.Infectiouspancreatitiswithdevelopmentofsepsis(occursinupto5%of
allpatientswithpancreatitis)
E. Portalveinthrombosis
HepaticEncephalopathy
Hepaticencephalopathydevelopswhenammoniaandtoxins,whichareusually
metabolized(detoxified)bytheliver,enterintothesystemiccirculation.Hepatic
encephalopathycanbediagnosedin50-70%ofpatientswithchronichepatic
failure.
I. Clinicalmanifestations
A.Hepatic encephalopathy manifests as mild changes in personality to
alteredmotorfunctionsand/orlevelofconsciousness.
B.Mostepisodesareprecipitatedbyidentifiablefactors,includinggastroin-
testinal bleeding, excessive protein intake, constipation, excessive
diuresis, hypokalemia, hyponatremia or hypernatremia, azotemia,
infection, poor compliance with lactulose therapy, sedatives (benzo-
diazepines,barbiturates,antiemetics),hepaticinsult(alcohol,drugs,viral
hepatitis),surgery,orhepatocellularcarcinoma.
C.Hepatic encephalopathy is a diagnosis of exclusion. Therefore, if a
patientwithacuteorchronicliverfailuresuddenlydevelopsalteredmental
status, concomitant problems must be excluded, such as intracranial
lesions (hemorrhage, infarct, tumor, abscess), infections (meningitis,
encephalitis, sepsis), metabolic encephalopathies (hyperglycemia or
hypoglycemia, uremia, electrolyte imbalance), alcohol intoxication or
withdrawal,Wernicke'sencephalopathy,drugtoxicity(sedatives,psycho-
activemedications),orpostictalencephalopathy.
D.Physicalexammayrevealhepatosplenomegaly,ascites,jaundice,spider
angiomas,gynecomastia,testicularatrophy,andasterixis.
E.Computedtomographymaybeusefultoexcludeintracranialabscessor
hemorrhage.Laboratoryevaluationmayincludeserumammonia,CBC,
electrolytepanel,liverprofile,INR/PTT,UA,andbloodcultures.
II. Treatmentofhepaticencephalopathy
A.Flumazenil (Romazicon) may transiently improve the mental state in
patientswithhepaticencephalopathy.Dosageis0.2mg(2mL)IVover30
seconds q1min until a total dose of 3 mg; if a partial response occurs,
HepaticEncephalopathy105
continue0.5mgdosesuntilatotalof5mg.Excessivedosesofflumazenil
mayprecipitateseizures.
B.Lactulose is a non-absorbable disaccharide, which decreases the
absorption of ammonia into the blood stream. Lactulose can be given
orally,throughanasogastrictube,orrectally(lesseffective).Thedosage
is 30-45 mL PO q1h x 3 doses, then 15-45 mL PO bid-qid titrate to
produce2-4softstools/d.Alaxativesuchasmagnesiumsulfateandan
enema are given before lactulose therapy is started. Lactulose enema
(300mLoflactulosein700mLoftapwater),250mLPRq6h.
C.Neomycin,apoorlyabsorbedantibiotic,altersintestinalfloraandreduces
thereleaseofammoniaintotheblood(initially1-2gorallyfourtimesa
day). Because chronic neomycin use can cause nephrotoxicity and
ototoxicity,neomycinshouldbeusedforshortperiodsoftime, and the
doseshouldbedecreasedto1-2g/dayafterachievementofthedesired
clinicaleffect.Alternatively,metronidazolecanbegivenat250mgorally
threetimesadayaloneorwithneomycin.
D.Dietaryproteinisinitiallywithheld,andintravenousglucoseisadminis-
teredtopreventexcessiveendogenousproteinbreakdown.Asthepatient
improves,dietaryproteincanbereinstatedatalevelof20gmperdayand
thenincreasedgraduallytoaminimumof60gmperday.Ifadequateoral
intakeofproteincannotbeachieved,therapywithoralorenteralformulas
ofcaseinhydrolysates(Ensure)oraminoacids(FreAmine)isindicated.
References
BessonI,etal:Sclerotherapywithorwithoutoctreotideforacutevaricealbleeding,NEng
JMed333(9):555-60,1995.
AdamsL;SoulenMC.TIPS:aNewAlternativefor the VaricealBleeder.AmJCritCare
2:196,1993.
Grate ND: Diagnosis and treatment of gastrointestinal bleeding secondary to protal
hypertension.AJG1997;92(7):1081-91
RiordanSM;WilliamsR:Treatmentofhepaticencephalopathy.NEJM1997;337(7):473-79
HaberPS;PerolaEC;WilsonJS:Clinicalupdate:managementofacutepancreatitis.Jof
hepatology1997;12(3):189-97
106HepaticEncephalopathy
PoisoningandDrugOverdose107
Toxicology
HansPoggemeyer,MD
PoisoningandDrugOverdose
I. Managementofpoisoninganddrugoverdose
A.Stabilizevitalsigns;maintainairway,breathingandcirculation.
B.Considerintubationifpatienthasdepressedmentalstatusandisatriskfor
aspirationorrespiratoryfailure.
C.EstablishIVaccessandadministeroxygen.
D.Drawbloodforbaselinelabs(seebelow).
E.If altered mental status is present, administer D50W 50 mL IV push,
followedbynaloxone(Narcan)2mgIV,followedbythiamine100mgIV.
II. Gastrointestinaldecontamination
A.Gastriclavage
1. Studies have challenged the safety and efficacy of gastric lavage.
Lavageretrieveslessthan30%ofthetoxicagentwhenperformed1
hourafteringestion.Gastriclavagemaypropeltoxinsintotheduode-
num,andaccidentalplacementofthetubeintothetracheaormainstem
bronchusmayoccur.
2. Gastric lavage may be considered if the patient has ingested a
potentiallylife-threateningamountofpoisonandtheprocedurecanbe
undertakenwithin60minutesofingestion.
3. Contraindications:Acid,alkali,orhydrocarbons.
4. PlacethepatientinTrendelenburg'spositionandleftlateraldecubitus.
Insertalargebore(32-40)frenchEwaldorogastrictube.AsmallerNG
tubemaybeusedbutmaybelesseffectiveinretrievinglargeparticles.
5. After tube placement has been confirmed by auscultation, aspirate
stomachcontentsandlavagewith200ccaliquotsofsalineorwater
until clear (up to 2 L). The first 100 cc of fluid should be sent for
toxicologyanalysis.
B.Activatedcharcoal
1. Activatedcharcoalisnoteffectiveforalcohols,aliphatichydrocarbons,
caustics,cyanide,elementalmetals(boricacid,iron,lithium,lead),or
pesticides.
2. Theoralornasogastricdoseis50gmmixedwithsorbitol.Thedose
should be repeated at 25-50 gm q4-6h for 24-48 hours if massive
ingestion, sustained release products, tricyclic antidepressants,
phenothiazines,sertraline(Zoloft),paroxetine(Paxil),carbamazepine,
digoxin, phenobarbital, phenytoin, valproate, salicylate, doxepin, or
theophyllinewereingested.
3. Giveoralcathartic(70%sorbitol)withcharcoal.
C.Wholebowelirrigation
1. Whole bowel irrigation can prevent further absorption in cases of
massive ingestion, delayed presentation, or in overdoses of enteric
coated or sustained release pills. This treatment may be useful in
eliminatingobjects,suchasbatteries,oringestedpacketsofdrugs.
2. AdministerGoLytely,orColyteorallyat1.6-2.0literperhouruntilfecal
effluentisclear.
108ToxicologicSyndromes
D.Hemodialysis:Indicationsincludeingestionofphenobarbital,theophylline,
chloral hydrate, salicylate, ethanol, lithium, ethylene glycol, isopropyl
alcohol,procainamide,andmethanol,orseveremetabolicacidosis.
E.Hemoperfusion: May be more effective than hemodialysis except for
bromides,heavymetals,lithium,andethyleneglycol.Hemoperfusionis
effectivefordisopyramide,phenytoin,barbiturates,theophylline.
ToxicologicSyndromes
I. Characteristicsofcommontoxicologicsyndromes
A. Cholinergicpoisoning:Salivation,bradycardia,defecation,lacrimation,
emesis,urination,miosis.
B. Anticholinergicpoisoning:Dryskin,flushing,fever,urinaryretention,
mydriasis,thirst,delirium,conductiondelays,tachycardia,ileus.
C. Sympathomimetic poisoning: Agitation, hypertension, seizure,
tachycardia,mydriasis,vasoconstriction.
D. Narcotic poisoning: Lethargy, hypotension, hypoventilation, miosis,
coma,ileus.
E. Withdrawal syndrome: Diarrhea, lacrimation, mydriasis, cramps,
tachycardia,hallucination.
F. Salicylatepoisoning:Fever,respiratoryalkalosis,ormixedacid-base
disturbance,hyperpnea,hypokalemia,tinnitus.
G. Causes of toxic seizures: Amoxapine, anticholinergics, camphor,
carbonmonoxide,cocaine,ergotamine,isoniazid,lead,lindane,lithium,
LSD, parathion, phencyclidine, phenothiazines, propoxyphene
propranolol, strychnine, theophylline, tricyclic antidepressants,
normeperidine(metaboliteofmeperidine),thiocyanate.
H. Causesoftoxiccardiacarrhythmias:Arsenic,beta-blockers,chloral
hydrate, chloroquine, clonidine, calcium channel blockers, cocaine,
cyanide, carbon monoxide, digitalis, ethanol, phenol, phenothiazine,
tricyclics.
I. Extrapyramidal syndromes: Dysphagia, dysphonia, trismus, rigidity,
torticollis,laryngospasm.
AcetaminophenOverdose
I. Clinicalfeatures
A.Acute lethal dose = 13-25 g. Acetaminophen is partly metabolized to
N-acetyl-p-benzoquinoniminewhichisconjugatedbyglutathione.Hepatic
glutathionestorescanbedepletedinacetaminophenoverdose,leadingto
centrilobularhepaticnecrosis.
B.Liver failure occurs 3 days after ingestion if untreated. Liver failure
presents with right upper quadrant pain, elevated liver function tests,
coagulopathy,hypoglycemia,renalfailureandencephalopathy.
II. Treatment
A.Gastrointestinal decontamination should consist of gastric lavage
followedbyactivatedcharcoal.Residualcharcoalshouldberemovedwith
salinelavagepriortogivingN-acetyl-cysteine(NAC).
AcetaminophenOverdose109
B.Checkacetaminophenlevel4hoursafteringestion.Anomogramshould
be used to determine if treatment is necessary (see next page). Start
treatmentiflevelisabovethenontoxicrangeorifthelevelispotentially
toxicbutthetimeofingestionisunknown.
C.Therapymuststartnolaterthan8-12hoursafteringestion.Treatmentafter
16-24 hours of non-sustained release formulation is significantly less
effective,butshouldstillbeaccomplished.
D.OralN-acetyl-cysteine(Mucomyst):140mg/kgPOfollowedby70mg/kg
POq4hx17doses(total1330mg/kgover72h).Repeatloadingdoseif
emesisoccursCompletealldosesevenafteracetaminophenlevelfalls
belowcriticalvalue.
E.Hemodialysisandhemoperfusionaresomewhateffective,butshouldnot
taketheplaceofNACtreatment.
5
15 2 0 2 5 3 0 35
1
2
3
4
5
7
8
2 0
3 0
4 0
5 0
7 0
8 0
9 0
1 50
2 00
2 50
3 00
9
Hours Post Ingest ion
6
1 0
6 0
1 00
10
INTERPRET A T ION OF ACTAMINOPHEN L E VEL
VS HOURS POST INGESTION
No risk of toxicity if underdouble lines.
Probable risk if abovetopline.
P oss ib l er is k i fb etwe en do ubl e li n es.
Out c ome is bes t iftr eat me nti si ni tiat ed with i n 1 2h ours o f
i nge s tion.
Gr a phapp l ies to non -s u sta ine d re l ea se formul ati o ns o nly .
110CocaineOverdose
CocaineOverdose
I. Clinicalevaluation
A.Cocainecanbeusedintravenously,smoked,ingested,orinhalednasally.
Streetcocaineofteniscutwithothersubstancesincludingamphetamines,
LSD,PCP,heroin,strychnine,lidocaine,talc,andquinine.
B.One-thirdoffatalitiesoccurwithin1hour,withanotherthirdoccurring6-24
hourslater.
C.Personsmaytransportcocainebyswallowingwrappedpackets,andsome
usersmayhastilyswallowpacketsofcocainetoavoidarrest.
II. Clinicalfeatures
A.CNS: Sympathetic stimulation, agitation, seizures, tremor, headache,
subarachnoidhemorrhage,ischemiccerebralstoke,psychosis,hallucina-
tions,fever,mydriasis,formication(sensationofinsectscrawlingonskin).
B.Cardiovascular: Atrial andventriculararrhythmias,myocardialinfarction,
hypertension,hypotension,myocarditis,aorticrupture,cardiomyopathy.
C.Pulmonary: Noncardiogenic pulmonary edema, pneumomediastinum,
alveolarhemorrhage,hypersensitivitypneumonitis,bronchiolitisobliterans.
D.Other:Rhabdomyolysis,mesentericischemia,hepatitis.
III. Treatment
A.Treatment consists of supportive care because no antidote exists. GI
decontamination, including repeated activated charcoal, whole bowel
irrigation and endoscopic evaluation is provided if oral ingestion is
suspected.
B.Hyperadrenergicsymptomsshouldbetreatedwithbenzodiazepines,such
aslorazepam.
C.Seizures:Treatwithlorazepam,phenytoin,orphenobarbital.
D.Arrhythmias
1. Treat hyperadrenergic state and supraventricular tachycardia with
lorazepamandpropranolol.
2. Ventriculararrhythmiasaretreatedwithlidocaineorpropranolol.
E.Hypertension
1. Uselorazepamfirstfortachycardiaandhypertension.
2. If noresponse,uselabetalolbecauseithasalphaandbetablocking
effects.
3. If hypertension remains severe, administer sodium nitroprusside or
esmololdrip.
F. Myocardialischemiaandinfarction:Treatwiththrombolysis,heparin,
aspirin, beta-blockers, nitroglycerin. Control hypertension and exclude
CNSbleedingbeforeusingthrombolytictherapy.
CyclicAntidepressantOverdose111
CyclicAntidepressantOverdose
I. Clinicalfeatures
A.Antidepressants have prolonged body clearance rates, and cannot be
removalbyforceddiuresis,hemodialysis,andhemoperfusion. Delayed
absorption is common because of decreased GI motility from
anticholinergic effects. Cyclic antidepressants undergo extensive
enterohepaticrecirculation.
B.CNS:Lethargy,coma,hallucinations,seizures,myoclonicjerks.
C.Anticholinergiccrises: Blurredvision,dilatedpupils,urinaryretention,
drymouth,ileus,hyperthermia.
D.Cardiac:Hypotension,ventriculartachyarrhythmias,sinustachycardia.
E.ECG:Sinustachycardia,rightbundlebranchblock,rightaxisdeviation,
increasedPRandQTinterval,QRS>100msec,orrightaxisdeviation.
Prolongation oftheQRSwidthisamorereliablepredictorofCNSand
cardiactoxicitythantheserumlevel.
II. Treatment
A.Gastrointestinaldecontaminationandsystemicdrugremoval
1. Magnesiumcitrate300mLvianasogastrictubex1dose.
2. Activatedcharcoalpremixedwithsorbitol50gmvianasogastrictube
q4-6haround-the-clockuntiltheserumleveldecreasestotherapeutic
range. Maintain the head-of-bed at a 30-45 degree angle to prevent
aspiration.
3. Cardiactoxicity
a. Alkalinizationisacardioprotectivemeasureandithasnoinfluence
ondrugelimination.Thegoaloftreatmentistoachieveanarterial
pHof7.50-7.55.Ifmechanicalventilationisnecessary,hyperventi-
latetomaintaindesiredpH.
b. Administer sodium bicarbonate 50-100 mEq (1-2 amps or 1-2
mEq/kg)IVover5-10min.Followedbyinfusionofsodiumbicarbon-
ate, 2 amps in 1 liter of D5W at 100-150 cc/h. Adjust IV rate to
maintaindesiredpH.
4. Seizures
a. AdministerlorazepamordiazepamIVfollowedbyphenytoin.
b. Physostigmine,1-2mgslowIVover3-4min,isnecessaryifseizures
continue.
DigoxinOverdose
I. Clinicalfeatures
A. Thetherapeuticwindowofdigoxinis0.8-2.0ng/mL.Drugsthatincrease
digoxin levels include verapamil, quinidine, amiodarone, flecainide,
erythromycin, and tetracycline. Hypokalemia, hypomagnesemia and
hypercalcemiaenhancedigoxintoxicity.
B. CNS:Confusion,lethargy;yellow-greenvisualhalo.
C. Cardiac: Common dysrhythmias include ventricular tachycardia or
fibrillation; variable atrioventricular block, atrioventricular dissociation;
sinusbradycardia,junctionaltachycardia,prematureventricularcontrac-
tions.
D. GI:Nausea,vomiting.
112EthyleneGlycolIngestion
E. Metabolic: Hypokalemia enhances the toxic effects of digoxin on the
myocardialtissueandmaybepresentinpatientsondiuretics.
II. Treatment
A. Gastrointestinaldecontamination:Gastriclavage,followedbyrepeated
dosesofactivatedcharcoal,iseffective;hemodialysisisineffective.
B. Treatbradycardiawithatropine,isoproterenol,andcardiacpacing.
C. Treat ventricular arrhythmias with lidocaine or phenytoin. Avoid
procainamideandquinidinebecausetheyareproarrhythmic andslowAV
conduction.
D. Electrical DC cardioversion may be dangerous in severe toxicity.
Hypomagnesemiaandhypokalemiashouldbecorrected.
E. Digibind(Digoxin-specificFabantibodyfragment)
1. Indication: Life-threatening arrhythmias refractory to conventional
therapy.
2. DosageofDigoxinimmuneFab:
(numberof40mgvials)=Digoxinlevel(ng/mL)xbodyweight(kg)
100
3. DissolvethedigoxinimmuneFabin100-150mLofNSandinfuseIV
over15-30minutes.A0.22micronin-linefiltershouldbeusedduring
infusion.
4. Hypokalemia,heartfailure,andanaphylaxismayoccur.Thecomplex
isrenallyexcreted;afteradministration,serumdigoxinlevelsmaybe
artificiallyhighbecausebothfreeandbounddigoxinismeasured.
EthyleneGlycolIngestion
I. Clinicalfeatures
A. Ethyleneglycolisfoundinantifreeze,detergents,andpolishes.
B. Toxicity: Half-life 3-5 hours; the half-life increases to 17 hours if
coingestedwithalcohol.Theminimallethaldoseis1.0-1.5cc/kg,andthe
lethalbloodlevelis200mg/dL.
C. Aniongapmetabolicacidosisandsevereosmolargapisoftenpresent.
CNS depression and cranial nerve dysfunction (facial and
vestibulocochlearpalsies)arecommon.
D. GIsymptomssuch as flankpain.Oxalatecrystalsmaybeseeninthe
urinesediment.Otherfindingsmayincludehypocalcemia(duetocalcium
oxalateformation);tetany,seizures,andprolongedQT.
II. Treatment
A. Fomepizole(Antizol)loadingdose15mg/kgIV;then10mg/kgIVq12h
x4,then15mg/kgIVq12huntilethyleneglycollevelis<20mg/dL.
B. Pyridoxine100mgIVqidx2daysandthiamine100mgIVqidx2days.
C. Ifdefinitivetherapyisnotimmediatelyavailable,3-4ouncesofwhiskey
(orequivalent)maybegivenorally.
D. Hemodialysis indications: Severe refractory metabolic acidosis,
crystalluria,serumethyleneglycollevel>50mg/dL;keepglycollevel<10
mg/dL.
Gamma-hydroxybutyrateIngestion113
Gamma-hydroxybutyrateIngestion
I. Clinicalfeatures
A. Gamma-hydroxybutyrate(GHB)wasusedasananestheticagentbutwas
bannedbecauseoftheoccurrenceofseizures.Gamma-hydroxybutyrate
is now an abused substance at dance clubs because of the euphoric
effects of the drug. It is also abused by body builders because of a
mistakenbeliefthatithasanabolicproperties.Gamma-hydroxybutyrate
isaclear,odorless,oily,saltyliquid.Itisrapidlyabsorbedwithin20-40
minutesofingestionandmetabolizedintheliver.Thehalf-lifeofGHBis
20-30min.
B. Gamma-hydroxybutyrate is not routinely included on toxicological
screens,butitcanbedetectedinthebloodandurinebygaschromatog-
raphywithin12hoursofingestion.Gammahydroxybutyratemaycause
respiratory depression, coma, seizures, and severe agitation. Cardiac
effectsincludehypotension,cardiacarrest,andseverevomiting.
II. Treatment
A. GastriclavageisnotindicatedduetorapidabsorptionofGHB.
B. Immediate care consists of support of ventilation and circulation.
Agitation should be treated with benzodiazepines, haloperidol, or
propofol. Seizures should be treated with lorazepam, phenytoin, or
valproicacid.
IronOverdose
I. Clinicalfeatures
A. ToxicityiscausedbyfreeradicalorgandamagetotheGImucosa,liver,
kidney,heart,andlungs.Thecauseofdeathisusuallyshockandliver
failure.
Toxicdosagesandserumlevels
Nontoxic <10-20mg/kgofelementaliron(0-100mcg/dL)
Toxic >20mg/kgofelementaliron(350-1000mcg/dL)
Lethal >180-300mg/kgofelementaliron(>1000mcg/dL)
B.Two hours after ingestion: Severe hemorrhagic gastritis; vomiting,
diarrhea,lethargy,tachycardia,andhypotension.
C.Twelvehoursafteringestion:Improvementandstabilization.
D.12-48 hours after ingestion: GI bleeding, coma, seizures, pulmonary
edema, circulatory collapse, hepatic and renal failure, coagulopathy,
hypoglycemia,andseveremetabolicacidosis.
II. Treatment
A.Administerdeferoxamineifironlevelsreachtoxicvalues.Deferoxamine
100mgbinds9mgoffreeelementaliron.Thedeferoxaminedosageis
10-15mg/kg/hrIVinfusion.
114IsopropylAlcoholIngestion
B.Treatuntil24hoursaftervinrosecoloredurineclears.Serumironlevels
duringchelationarenotaccurate.Deferoxaminecancausehypotension,
allergic reactions such as pruritus, urticarial wheals, rash, anaphylaxis,
tachycardia,fever,andlegcramps.
C.Gastrointestinaldecontamination
1. Charcoalisnoteffectiveinabsorbingelementaliron.Abdominal x-rays
shouldbeevaluatedforremainingirontablets.Considerwholebowel
lavage if iron pills are past the stomach and cannot be removed by
gastriclavage(seepage105).
2. Hemodialysisisindicatedforseveretoxicity.
IsopropylAlcoholIngestion
I. Clinicalfeatures
A. Isopropylalcoholisfoundinrubbingalcohol,solvents,andantifreeze.
B. Toxicity:Lethaldose:3-4g/kg
1. Lethalbloodlevel:400mg/dL
2. Half-life=3hours
C. Metabolism: Isopropyl alcohol is metabolized to acetone. Toxicity is
characterizedbyananiongapmetabolicacidosiswithhighserumketone
level;mildosmolargap;mildlyelevatedglucose.
D. CNS depression, headache, nystagmus; cardiovascular depression,
abdominalpainandvomiting,andpulmonaryedemamayoccur.
II.Treatment
A. Treatmentconsistsofsupportivecare.Noantidoteisavailable;ethanolis
notindicated.
B. Hemodialysis:Indications:refractoryhypotension,coma,potentiallylethal
bloodlevels.
LithiumOverdose
I. Clinicalfeatures
A. Lithiumhasanarrowtherapeuticwindowof0.8-1.2mEq/L.
B. Drugs that will increase lithium level include NSAIDs, phenothiazines,
thiazideandloopdiuretics(bycausinghyponatremia).
C. Toxicity
1.5-3.0mEq/L=moderatetoxicity
3.0-4.0mEq/L=severetoxicity
D. Toxicityinchroniclithiumusersoccursatmuchlowerserumlevelsthan
withacuteingestions.
E. Commonmanifestationsincludeseizures,encephalopathy,hyperreflexia,
tremor,nausea,vomiting,diarrhea,hypotension.Nephrogenicdiabetes
insipidus and hypothyroidism may also occur. Conduction block and
dysrhythmiasarerare,but reversibleT-wavedepressionmayoccur.
II.Treatment
A. Correct hyponatremia with aggressive normal saline hydration. Follow
lithiumlevelsuntil<1.0mEq/L.
MethanolIngestion115
B. Forcedsolutediuresis:Hydratewithnormalsalineinfusiontomaintain
urineoutputat2-4cc/kg/hr;usefurosemide(Lasix)40-80mgIVdosesas
needed.
C. GIdecontamination
1. Administer gastric lavage. Activated charcoal is ineffective. Whole
bowelirrigationmaybeuseful.
2. Indicationsforhemodialysis:Level>4mEq/L;CNSorcardiovascular
impairmentwithlevelof2.5-4.0mEq/L.
MethanolIngestion
I. Clinicalfeatures
A. Methanolisfoundinantifreeze,Sterno,cleaners,andpaints.
B. Toxicity
1. 10cccausesblindness
2. Minimallethaldose=1-5g/kg
3. Lethalbloodlevel=80mg/dL
4. Symptomaticin40minutesto72hours.
C. SignsandSymptoms
1. Severeosmolarandaniongapmetabolicacidosis.
2. Visual changes occur because of optic nerve toxicity, leading to
blindness.
3. Nausea, vomiting, abdominal pain, pancreatitis, and altered mental
status.
II.Treatment
A. Ethanol10%isinfuseinD5Was7.5cc/kgloadthen1.4cc/kg/hdripto
keepbloodalcohollevelbetween100-150mg/dL.Continuetherapyuntil
themethanollevelisbelow20-25mg/dL.
B. Givefolate50mgIVq4htoenhanceformicacidmetabolism.
C. Correctacidosisandelectrolyteimbalances.
D. Hemodialysis:Indications:peakmethanollevel>50mg/dL;formicacid
level>20mg/dL;severemetabolicacidosis;acuterenalfailure;anyvisual
compromise.
SalicylateOverdose
I. Clinicalfeatures
A. Toxicity
150-300mg/kg-mildtoxicity
300-500mg/kg-moderatetoxicity
>500mg/kg-severetoxicity
B. Chronicusecancausetoxicityatmuchlowerlevels(ie,25mg/dL)than
occurswithacuteuse.
C. Acid/Base Abnormalities: Patients present initially with a respiratory
alkalosisbecauseofcentralhyperventilation.Laterananiongapmetabolic
acidosisoccurs.
D. CNS:Tinnitus,lethargy,irritability,seizures,coma,cerebraledema.
E. GI:Nausea,vomiting,liverfailure,GIbleeding.
116TheophyllineToxicity
F. Cardiac: Hypotension, sinus tachycardia, AV block, wide complex
tachycardia.
G. Pulmonary:Non-cardiogenicpulmonaryedema,adultrespiratorydistress
syndrome.
H. Metabolic: Renalfailure;coagulopathybecauseofdecreasedfactorVII;
hyperthermia because of uncoupled oxidative phosphorylation.
Hypoglycemiamayoccurinchildren,butitisrareinadults.
II.Treatment
A. Provide supportive care and GI decontamination. Aspirin may form
concretionsordrugbezoars,andingestionofentericcoatedpreparations
mayleadtodelayedtoxicity.
B. Multiple dose activated charcoal, whole bowel irrigation, and serial
salicylatelevelsareindicated.Hypotensionshouldbetreated vigorously
with fluids. Abnormalities should be corrected, especially hypokalemia.
Urineoutputshouldbemaintainedat200cc/hormore.Metabolicacidosis
shouldbetreatedwithbicarbonate50-100mEq(1-2amps)IVP.
C. Renalclearanceisincreasedbyalkalinizationofurinewithabicarbonate
infusion(2-3ampsin1literofD5WIVat150-200mL/h),keepingtheurine
pHat7.5-8.5.
D. Hemodialysisis indicatedforseizures,cardiacorrenalfailure,intractable
acidosis, acute salicylate level >120 mg/dL or chronic level >50 mg/dL
(therapeuticlevel15-25mg/dL).
TheophyllineToxicity
I. Clinicalfeatures
A. Drug interactions can increase serum theophylline level, including
quinolone and macrolide antibiotics, propranolol, cimetidine, and oral
contraceptives.Liverdiseaseorheartfailurewilldecreaseclearance.
B. Serumtoxicitylevels
20-40mg/dL- mild
40-70mg/dL- moderate
>70mg/dL-lifethreatening
C. Toxicityinchronicusersoccursatlowerserumlevelsthanwithshort-term
users. Seizures and arrhythmias can occur at therapeutic or minimally
supra-therapeuticlevels.
D. CNS:Hyperventilation,agitation,andtonic-clonicseizures.
E. Cardiac:Sinustachycardia,multi-focalatrialtachycardia,supraventricular
tachycardia,ventriculartachycardiaandfibrillation,prematureventricular
contractions,hypotensionorhypertension.
F. Gastrointestinal:Vomiting,diarrhea,hematemesis.
G. Musculoskeletal:Tremor,myoclonicjerks
H. Metabolic:Hypokalemia,hypomagnesemia,hypophosphatemia,hyper-
glycemia,andhypercalcemia.
II. Treatment
A. Gastrointestinaldecontaminationandsystemicdrugremoval
1. Activatedcharcoalpremixedwithsorbitol,50gmPOorvianasogastric
tube q4h around-the-clock until theophylline level is less than 20
mcg/mL. Maintain head-of-bed at 30 degrees to prevent charcoal
aspiration.
WarfarinOverdose117
2. Hemodialysis is as effective as repeated oral doses of activated
charcoal and should be used when charcoal hemoperfusion is not
feasible.
3. Indications for charcoal hemoperfusion: Coma, seizures,
hemodynamic instability, theophylline level >60 mcg/mL; rebound in
serumlevelsmayoccurafterdiscontinuationofhemoperfusion.
4. Seizures are generally refractory to anticonvulsants. High doses of
lorazepam,diazepamorphenobarbitalshouldbeused;phenytoinis
lesseffective.
5. Treatmentofhypotension
a. Normalsalinefluidbolus.
b. Norepinephrine8-12mcg/minIVinfusionor
c. Phenylephrine20-200mcg/minIVinfusion.
6. Treatmentofventriculararrhythmias
a. Amiodarone150-300mgIVover10min,then1mg/minx6hours,
followedby0.5mg/minIVinfusion.Lidocaineshouldbeavoided
becauseithasepileptogenicproperties.
b. Esmolol (Brevibloc) 500 mcg/kg/min loading dose, then 50-300
mcg/kg/mincontinuousIVdrip.
Warfarin(Coumadin)Overdose
I. Clinicalmanagement
A. Eliminationmeasures:Gastriclavageandactivatedcharcoalifrecent
oralingestionofwarfarin(Coumadin).
B. Reversal of coumadin anticoagulation: Coagulopathy should be
correctedrapidlyorslowlydependingonthefollowingfactors:1)Intensity
ofhypocoagulability,2)severityorriskofbleeding,3)needforreinstitution
ofanticoagulation.
C. Emergentreversal
1. Freshfrozenplasma:ReplacevitaminKdependentfactorswithFFP
2-4units;repeatin4hoursifprothrombintimeremainsprolonged.
2. VitaminK,25mgin50ccNS,toinfusenofasterthan1mg/min;risk
ofanaphylactoidreactionsandshock;slowinfusionminimizesrisk.
D. Reversalover24-48Hours: VitaminK10-25mgsubcutaneously.Full
reversal of anticoagulation will result in resistance to further Coumadin
therapyforseveraldays.
E. Partial correction: Lower dose vitamin K (0.5-1.0 mg) will lower
prothrombintimewithoutinterferingwithreinitiationofCoumadin.
References
CraigK.GomezH,etal:SevereGamma-HydroxybutyrateWithdrawal:Acasereportand
literaturereview.JofEmergencyMedicine,2000;18:65-70.
The American Academy of Clinical Toxicology and the European Association of Poison
ControlCentersandClinicalToxicologistspositionstatementongutdecontaminationin
acutepoisoning.JToxicol-ClinToxicol1997;35:695-762.
Kelly RA, Smith TW: Recognition and management of digitalis toxicity. The American
JournalofCardiology,69:108G,1992
MarkensonD,GreenbergMD:CyclicAntidepressantoverdose:mechanismtomanagement.
EmergencyMedicine,25:49,1993.
118WarfarinOverdose
Spiller HA, Kreuzelok EP, Grand GA, et al.: A prospective evaluation of the effect of
activatedcharcoalbeforeoraln-acetylcysteineinacetaminophenoverdose.Annalsof
EmergencyMedicine,23:519-523,1994.
IschemicStroke119
Neurologic Disorders
HansPoggemeyer,MD
IschemicStroke
IschemicstrokeisthethirdleadingcauseofdeathintheUnitedStatesandthe
mostcommoncauseofneurologicdisabilityinadults.Approximately85percent
ofstrokesareischemicinnature.
I. Clinicalevaluationofthestrokepatient
A. Arapidevaluationshoulddeterminethetimewhensymptomsstarted.
Other diseases that may mimic a stroke, such as seizure disorders,
metabolicabnormalities,hypoglycemia,complexmigraine,dysrhythmia
orsyncope,infection,shouldbeexcluded.
B. Markers of vascular disease such as diabetes, angina pectoris and
intermittentclaudication,aresuggestiveofischemicstroke.Ahistoryof
atrialfibrillationorMIsuggestsacardiacembolicstroke.
II. Physicalexamination
A. Assessmentshoulddeterminewhetherthepatient'sconditionisacutely
deterioratingorrelativelystable.Airwayandcirculatorystabilizationtake
precedenceoverdiagnosticandtherapeuticinterventions.
B. Neurologicexam.Evaluationshouldincludethelevel ofconsciousness,
orientation; ability to speak and understand language; cranial nerve
function, especially eye movements, pupil reflexes and facial paresis;
neglect,gazepreference,armandlegstrength,sensation,andwalking
ability.
C. Asemiconsciousorunconsciouspatientprobablyhasahemorrhage.A
patient with an ischemic stroke may be drowsy but is unlikely to lose
consciousnessunlesstheinfarctedareaislarge.
III. CTscanninganddiagnosticstudies
A. AllpatientswithsignsofstrokeshouldundergoanoncontrastheadCT
toscreenforbleedingandtorule outexpandinglesions,suchassubdural
hematomas,orepiduralhematomas.
B. CTscanningusuallydoesnotshowsignsofacuteischemia.Within3
hoursofonset,thesensitivityis30%,within24hours60%,and100%at
7 days. Early CT changes include effacement of sulci or ventricles,
blurringofthebasalganglia,masseffect,andlossofthenormalgray-
whitejunctionintheinsula.
C. Acompletebloodcountincludingplatelets,internationalnormalizedratio,
activated partial thromboplastin time, serum electrolytes, and a rapid
blood glucose should be obtained. ECG, and chest x-ray should be
ordered.Arterial bloodgasandlumbarpunctureshouldbeobtainedwhen
indicated.
IV. Managementofischemicstroke
A. Tissueplasminogenactivator(t-PA,Activase).Useoft-PAwithin3
hoursofonsetofstrokeresultsincompleteornear-completeneurological
recovery inone-thirdmorepatients,comparedtoplacebo,atthreeand12
months.Theincidenceofbrainhemorrhageis10timeshigherwitht-PA
(6.4%vs0.6%placebo)andoccurspredominantlyinthosepatientswith
120IschemicStroke
gross neurological deficit, and in the presence of cerebral edema or
mass.
B. TheCTscanmustdocumenttheabsenceofintracranialbleedingbefore
treatment.
CriteriaforThrombolysisofPatientswithAcuteIschemicStroke
UsingTissuePlasminogenActivator
Inclusioncriteria
Agegreaterthan18years
Clinicaldiagnosisofischemicstroke,withonsetofsymptomswithinthree
hoursofinitiationoftreatment
NoncontrastCTscanwithnoevidenceofhemorrhage
Exclusioncriteria
History
Strokeorheadtraumainpreviousthreemonths
Historyofintracranialhemorrhagethatmayincreaseriskofrecurrent
hemorrhage
Majorsurgeryorotherserioustraumainprevious14days
Gastrointestinalorgenitourinarybleedinginprevious21days
Arterialpunctureinprevioussevendays
Pregnantorlactatingpatient
Clinicalfindings
Rapidlyimprovingstrokesymptoms
Seizureatonsetofstroke
Symptomssuggestiveofsubarachnoidhemorrhage,evenifCTscanis
normal
Persistentsystolicpressuregreaterthan185mmHgordiastolicpres-
suregreaterthan110mmHg,orpatientisrequiringaggressivetherapy
tocontrolbloodpressure
Clinicalpresentationconsistentwithacutemyocardialinfarctionor
postmyocardialinfarctionpericarditisrequirescardiologicevaluation
beforetreatment
Imagingresults
CTscanwithevidenceofhemorrhage
CTscanwithevidenceofhypodensityand/oreffacementofcerebralsulci
inmorethanone-thirdofmiddlecerebralarteryterritory
Laboratoryfindings
Glucoselevellessthan50mgperdLorgreaterthan400mgperdL
Plateletcountlessthan100,000permm
3
Warfarintherapywithaninternationalnormalizedratio$1.7
Patienthasreceivedheparinwithin48hours,andpartialthromboplastin
timeisincreased
IschemicStroke121
AntiplateletAgentsforPreventionofIschemicStoke
Enteric-coatedaspirin(Ecotrin)325mgPOqd
Clopidogrel(Plavix)75mgPOqd
Extended-releaseaspirin25mgwithdipyridamole200mg(Aggrenox)
onetabPOqd
C.Antiplateletagentsminimallyreduceintheriskofdeathordisabilityby
about one case per 100 patients. Aspirin, clopidogrel (Plavix), or a
combination of low-dose aspirin plus extended-release dipyridamole
(Aggrenox)shouldbeinitiatedafterarepeatCTscan(24hoursaftert-
PA)hasexcludedhemorrhageduetothrombolysis.
D.Antithrombotictherapy.Heparinhasnoprovenbenefitinthetreatment
ofischemicstroke.Incasesofcardioembolicstrokeorcarotidstenosis,
heparinmaybeinitiated24hoursaftert-PA,providingarepeatCTscan
at that time shows no hemorrhage. Heparin should be gradually
transitionedtowarfarinforlong-termtreatment.
E.Cytoprotectiveagents.Theseagentsincreasethetoleranceofneurons
toischemia.Largetrialsevaluatingciticoline,clomethiazoleandglycine
antagonistshouldbecompletedsoon.
InitialManagementofAcuteStroke
Determinewhetherstrokeisischemicorhemorrhagicbycomputed
tomography
Consideradministrationoft-PAiflessthanthreehoursfromstrokeonset
Generalmanagement:
Bloodpressure(avoidhypotension)
Assureadequateoxygenation
Administerintravenousglucose
Takedysphagia/aspirationprecautions
Considerprophylaxisforvenousthrombosisifthepatientisunableto
walk
Suppressfever,ifpresent
Assessstrokemechanism(eg,atrialfibrillation,hypertension)
Consideraspirinorclopidogrel(Plavix)therapyifischemicstrokeand
nocontraindications(begin24hoursaftert-PA).
F. Thrombolytictherapy.Thedoseoft-PAforacuteischemicstrokeis0.9
mg/kgwithamaximumdoseof90mg.Tenpercentofthedoseisgiven
asabolusdose,andtheremainderisgivenover60minutes.Noheparin
or anti-platelet agents (aspirin) should be administered until 24 hours
afterinitiationoft-PAtreatmentandascan24hoursafterthestrokeCT
hasruledoutintracranialhemorrhage.
G. Bloodpressuremanagementinthrombolytictherapy
1. Arterialbloodpressureshouldbekeptjustbelow185mmHgduring
thefirst24hours.
2. Severehypertensionshouldbecontrolledwithlabetalol,administered
at an initial dose of 10 mg IV over 1-2 minutes. The dose may be
repeatedordoubledevery10-20minutesifneeded,oranIVinfusion
122ElevatedIntracranialPressure
of2mg/minmaybeinitiated.Iftheresponseisunsatisfactory,thenan
infusion of sodium nitroprusside starting at an initial dose of 0.1
mcg/kg/minisrecommended.
ElevatedIntracranialPressure
Cerebrospinal fluid (CSF) pressure in excess of 250 mm CSF is usually a
manifestationofseriousneurologicdisease.Intracranialhypertensionismost
oftenassociatedwithrapidlyexpandingmasslesions,CSFoutflowobstruction,
orcerebralvenouscongestion.
I. Clinicalevaluation
A. Increased intracranial pressure may manifest as headache caused by
tractiononpain-sensitivecerebralbloodvesselsorduramater.
B. PapilledemaisthemostreliablesignofICP,althoughitfailstodevelop
inmanypatientswithincreased ICP.Retinalvenouspulsations,when
present,implythatCSFpressureisnormalornotsignificantlyelevated.
PatientswithincreasedICPoftencomplainofworseningheadache,inthe
morning.
CausesofIncreasedIntracranialPressure
Diffusecerebraledema
Meningitis
Encephalitis
Hepaticencephalopathy
Reye'ssyndrome
Acuteliverfailure
Electrolyteshifts
Dialysis
Hypertensiveencephalopathy
Posthypoxicbraininjury
Leadencephalopathy
Uncompensatedhypercarbia
Headtrauma
Diffuseaxonalinjury
Space-occupyinglesions
Intracerebralhemorrhage
Epiduralhemorrhage
Subduralhemorrhage
Tumor
Abscess
Hydrocephalus
Subarachnoidhemorrhage
Meningitis
Aqueductalstenosis
Idiopathic
Miscellaneous
Pseudotumorcerebri
Craniosynostosis
Venoussinusthrombosis
II. IntracranialPressureMonitoring
A. ClinicalsignsofelevatedICP,suchastheCushingresponse(systemic
hypertension,bradycardia,andirregularrespirations),areusuallyalate
findings and may never even occur; therefore, ICP should be directly
measuredwithaninvasivedevice.
B. Normalintracranialpressuresrangefromapproximately10-20cmH
2
O(or
about5to15mmHg).Ventricularcatheterizationinvolvesinsertionofa
sterilecatheterintothelateralventricle.
ElevatedIntracranialPressure123
TreatmentofElevatedIntracranialPressure
Treatment Dose Advantages Limitations
Hypocarbia by
hyperventilation
pCO
2
25 to 33
mm Hg respira-
toryrateof10to
16/min
Immediateonset,well
tolerated
Hypotension,barotrauma,
durationusuallyhoursor
less
Osmotic Mannitol0.5to1
g/kgIVpush
Ra p i d o n s e t ,
titratable,predictable
Hypot ension, hypo-
kalemia,durationhoursor
days
Barbiturates Pentobarbital 25
mg/kg slow IV
infusionover3-4
hours
Mutes BP and respi-
ratoryfluctuations
Hypotension,fixedpupils
(small),durationdays
Hemicraniectomy Timingcritical Large sustainedICP
reduction
Surgical risk, ti ssue
herniationthroughwound
III. Treatmentofincreasedintracranialpressure
A. Positioningthepatientinanuprightpositionwiththeheadofthebedat
30degreeswilllowerICP.
B. HyperventilationisthemostrapidandeffectivemeansofloweringICP,
buttheeffectsareshortlivedbecausethebodyquicklycompensates.
ThepCO
2
shouldbemaintainedbetween25-33mmHg
C. Mannitolcanquickly lowerICP,althoughtheeffectisnotlonglastingand
mayleadtodehydrationorelectrolyteimbalance.Dosageis0.5-1gm/kg
(37.5-50gm)IVq6h;keeposmolarity<315;donotgiveformorethan
48h.
D. CorticosteroidsarebestusedtotreatincreasedICPinthesettingof
vasogenicedemacausedbybraintumorsorabscesses;however,these
agentshavelittlevalueinthesettingofstrokeorheadtrauma.Dosage
isdexamethasone(Decadron)10mgIVorIM,followedby4-6mgIV,IM
orPOq6h.
E. BarbituratecomaisusedformedicallyintractableICPelevationwhen
other medical therapies have failed. There is a reduction in ICP by
decreasingcerebralmetabolism.Thepentobarbitalloading doseis25
mg/kgbodyweightover3-4hours,followedby2-3mg/kg/hrIVinfusion.
Blood levels are periodically checked and adjusted to 30-40 mg/dL.
Patientsrequiremechanicalventilation,intracranialpressuremonitoring,
andcontinuouselectroencephalographicmonitoring.
F. Managementofbloodpressure.Beta-blockersormixedbetaandalpha
blockers provide the best antihypertensive effects without causing
significantcerebralvasodilatationthatcanleadtoelevatedICP.
124StatusEpilepticus
StatusEpilepticus
Status epilepticus (SE) is defined as a continuous seizures lasting at least 5
minutes, or 2 or more discrete seizures between which there is incomplete
recoveryofconsciousness.Simpleseizuresarecharacterizedbyfocalmotoror
sensory phenomena, with full preservation of consciousness. Generalized
seizures include generalized tonic-clonic seizures. Complex seizures are
diagnosedwhenanalterationinconsciousnesshasoccurred.
I. Diagnosticevaluation
A. Laboratoryevaluation
1. CBC,bloodglucoselevel,serumelectrolytes(sodium,magnesium,
calcium),anticonvulsantdruglevels,andurinalysis.
2. Lumbarpunctureisnecessaryifmeningitisorsubarachnoidhemor-
rhageissuspected.
3. Toxicologicscreeningisindicatedinspecificsituations.
B.CT scan is indicated if tumor, abscess, subarachnoid hemorrhage, or
traumaissuspected,orifthepatienthasnopriorhistoryofseizures.
C.Electroencephalogram.AnimmediateEEGmayberequiredifthepatient
failstoawakenpromptlyaftertheseizure.
EtiologyofStatusEpilepticus
Statusepilepticusinapatientwithahistoryofseizuredisorder
Noncompliancewithprescribedmedicalregimen
Withdrawalseizuresfromanticonvulsants
Breakthroughseizures
Newonsetseizuredisorderpresentingwithstatusepilepticus
Statusepilepticussecondarytomedical,toxicologic,orstructural
symptoms
Anoxicbraininjury
Strokesyndromes
Subarachnoidhemorrhage
Intracranialtumor
Trauma
Theophylline,cocaine,amphetamineorisoniazidoverdose;alcohol
withdrawal,gammahydroxybutyrate
Hyponatremia,hypernatremia,hypercalcemia,hypomagnesemia,
hepaticencephalopathy
Meningitis,brainabscess,encephalitis,CNScysticercosisor
toxoplasmosis
II. Managementofgeneralizedconvulsivestatusepilepticus(GCSE)
A. A history should be obtained, and a brief physical examination per-
formed. Initial stabilization consists of airway management, 100%
oxygenbymask,rapidglucosetesting,intravenousaccess,andcardiac
andhemodynamicmonitoring.
StatusEpilepticus125
B.Initialpharmacologictherapy
1. Thiamine100mgIVpushanddextrose50%water(D5W)50mLIV
push.
2. Lorazepam(Ativan)0.1mg/kgIVat2mg/min.Thesamedosemay
be repeated once. Lorazepam may be given IM if the IV route is
unavailable.
3. Phenytoinmaybeusedwhenbenzodiazepinesarenoteffective.The
loadingdoseofphenytoinis20mg/kgIV,followedby4-5mg/kg/day
(100mgIVq8hor200mgIVq12h);maximumrateforeachdoseis
50 mg/min in normal saline only. An additional loading dose of
phenytoin10mg/kgmaybegivenifnecessary.
4. Fosphenytoin(Cerebyx)is awatersolubleprodrugofphenytoin.The
advantages of fosphenytoin are faster loading and greater ease of
administration.Thedoseoffosphenytoinisexpressedinphenytoin
equivalents(PE).Theloadingdoseis20mgPE/kgIVat150mg/min,
followedby100mgPEIVq8h.FosphenytoinmaybegivenIVorIM
innormalsalineorD5W.
C.Refractorystatusepilepticus
1. Intubationshouldbeaccomplishedandbloodpressuresupportshould
bemaintainedwithfluidsandpressoragents.EEGmonitoringshould
beinitiated.
2. Midazolam (Versed) should be administered if seizures continue.
Loadingdoseis0.2mg/kg,followedby0.045mg/kg/hr.Titrateto0.6
mg/kg/hr.
3. Propofol(Diprivan)maybeusedifmidazolam(Versed)isineffective.
Loading dose is 1-2 mg/kg, followed by 2 mg/kg/hr, titrate to 10
mg/kg/hr. Adjust dose to achieve seizure-free status on EEG
monitoring.
4. Phenobarbitalmaybeadministeredasanalternativetoanesthetics
ifthepatientisnothypoxemicorhyperthermicandseizureactivityis
intermittent.Theloadingdoseis20mg/kgat75mg/min,then2mg/kg
IVq12h.
References
BrottT,etal.TreatmentofAcuteIschemicStroke.NEnglJMed2000;343:710-722.
LowensteinDH,etal.Statusepilepticus.NEnglJMed1998;338:970-976.
126StatusEpilepticus
DiabeticKetoacidosis127
Endocrinologic and Nephrologic
Disorders
MichaelKrutzik,MD
GuyFoster,MD
DiabeticKetoacidosis
Diabeticketoacidosisisdefinedbyhyperglycemia,metabolicacidosis,and
ketosis.
I. Clinicalpresentation
A. Diabetesisnewlydiagnosedin20%ofcasesofdiabeticketoacidosis.In
patients with known diabetes, precipitating factors include infection,
noncompliance with insulin, myocardial infarction, and gastrointestinal
bleeding.
B. Symptoms of DKA include polyuria, polydipsia, fatigue, nausea, and
vomiting,developingover1to2days.Abdominalpainisprominentin
25%.
C. Physicalexamination
1. Patients are typically flushed, tachycardic, tachypneic, and volume
depletedwithdrymucousmembranes.Kussmaul'srespiration(rapid,
deepbreathingandairhunger)occurswhentheserumpHisbetween
7.0and7.24.
2. A fruity odor on the breath indicates the presence of acetone, a
byproductofdiabeticketoacidosis.
3. Fever,althoughseldompresent,indicatesinfection.Eightypercentof
patientswithdiabeticketoacidosishavealteredmentalstatus.Most
areawakebutconfused;10%arecomatose.
D. Laboratoryfindings
1. Serumglucoselevel>300mg/dL
2. pH<7.35,pCO2<40mmHg
3. Bicarbonatelevelbelownormalwithanelevatedaniongap
4. Presenceofketonesintheserum
II. Differentialdiagnosis
A. Differentialdiagnosisofketosis-causingconditions
1. Alcoholicketoacidosisoccurswithheavydrinkingandvomiting.It
doesnotcauseanelevatedglucose.
2. Starvation ketosis occurs after 24 hours without food and is not
usually confused with DKA because glucose and serum pH are
normal.
B. Differentialdiagnosisofacidosis-causingconditions
1. Metabolic acidoses are divided into increased anion gap (>14
mEq/L)andnormalaniongap;aniongap=sodium-(CI- +HCO
3-
).
2. Aniongapacidosescanbecausedbyketoacidoses,lacticacidosis,
uremia,salicylate,methanol,ethanol,orethyleneglycolpoisoning.
3. Non-aniongapacidosesareassociatedwithanormalglucoselevel
and absent serum ketones. Causes of non-anion gap acidoses
includerenalorgastrointestinalbicarbonateloss.
128DiabeticKetoacidosis
C. Hyperglycemiacausedbyhyperosmolarnonketoticcomaoccursin
patients with type 2 diabetes with severe hyperglycemia. Patients are
usuallyelderlyandhaveaprecipitatingillness.Glucoselevelismarkedly
elevated(>600mg/dL),osmolarityisincreased,andketosisisminimal.
III. Treatmentofdiabeticketoacidosis
A. Fluidresuscitation
1. Fluiddeficitsaverage5litersor50mL/kg.Resuscitationconsistsof
1literofnormalsalineoverthefirsthourandasecondliteroverthe
secondandthirdhours.Thereafter, normalsalineshouldbeinfused
at100-120mL/hr.
2. Whentheglucoseleveldecreasesto250mg/dL,5%dextroseshould
be added to the replacement fluids to prevent hypoglycemia. If the
glucoseleveldeclinesrapidly,10%dextroseshouldbeinfusedalong
withregularinsulinuntiltheaniongapnormalizes.
B. Insulin
1. Aninitialloadingdoseconsistsof 0.1U/kgIVbolus.Insulinisthen
infusedat0.1U/kgperhour.Thebiologichalf-lifeofIVinsulinisless
than20minutes.Theinsulininfusionshouldbeadjustedeachhourso
thattheglucosedeclinedoesnotexceed100mg/dLperhour.
2. The insulin infusion rate may be decreased when the bicarbonate
levelisgreaterthan20mEq/L,theaniongapislessthan16mEq/L,
ortheglucoseis<250mg/dL.
C. Potassium
1. ThemostcommonpreventablecauseofdeathinpatientswithDKA
ishypokalemia.Thetypicaldeficitisbetween300and500mEq.
2. Potassiumchlorideshouldbestartedwhenfluidtherapyisstarted.In
mostpatients,theinitialrateofpotassiumreplacementis20mEq/h,
buthypokalemiarequiresmoreaggressivereplacement(40mEq/h).
3. Allpatientsshouldreceivepotassiumreplacement,exceptforthose
withrenalfailure,nourineoutput,oraninitialserumpotassiumlevel
greaterthan6.0mEq/L.
D. Sodium.Forevery100mg/dLthatglucoseiselevated,thesodiumlevel
shouldbeassumedtobehigherthanthemeasuredvalueby1.6mEq/L.
E. Phosphate. Diabetic ketoacidosis depletes phosphate stores. Serum
phosphate level should be checked after 4 hours of treatment. If it is
below 1.5 mg/dL, potassium phosphate should be added to the IV
solutioninplaceofKCl.
F. BicarbonatetherapyisnotrequiredunlessthearterialpHvalueis<7.0.
ForapHof<7.0,add50mEqofsodiumbicarbonatetothefirstliterofIV
fluid.
G. Magnesium. The usual magnesium deficit is 2-3 gm. If the patient's
magnesiumlevelislessthan1.8mEq/Loriftetanyispresent,magne-
sium sulfate is given as 5g in 500 mL of 0.45% normal saline over 5
hours.
H. Additionaltherapies
1. Anasogastrictubeshouldbeinsertedinsemiconsciouspatientsto
protectagainstaspiration.
2. Deep vein thrombosis prophylaxis with subcutaneous heparin
should be provided for patients who are elderly, unconscious, or
severelyhyperosmolar(5,000Uevery12hours).
DiabeticKetoacidosis129
IV. Monitoringoftherapy
130RenalFailure
A. Serum bicarbonate level and anion gap should be monitored to
determinetheeffectivenessofinsulintherapy.
B. Glucoselevelsshouldbecheckedat1-2hourintervalsduringIVinsulin
administration.
C. Electrolyte levels should be assessed every 2 hours for the first 6-8
hours, and then q8h. Phosphorus and magnesium levels should be
checkedafter4hoursoftreatment.
D. Plasma and urine ketones are helpful in diagnosing diabetic
ketoacidosis,butarenotnecessaryduringtherapy.
V. Determiningtheunderlyingcause
A. Infection is the underlying cause of diabetic ketoacidosis in 50% of
cases.Infectionoftheurinarytract,respiratorytract,skin,sinuses,ears,
orteethshouldbesought.Feverisunusualindiabeticketoacidosisand
indicates infection when present. If infection is suspected, antibiotics
shouldbepromptlyinitiated.
B. Omission of insulin doses is often a precipitating factor. Myocardial
infarction,ischemicstroke,andabdominalcatastrophesmayprecipitate
DKA.
VI. Initiationofsubcutaneousinsulin
A. Whentheserumbicarbonateandaniongaplevelsarenormal,subcuta-
neousregularinsulincanbestarted.
B. Intravenousandsubcutaneousadministrationofinsulinshouldoverlap
toavoidredevelopmentofketoacidosis.Theintravenousinfusionmaybe
stopped1hourafterthefirstsubcutaneousinjectionofinsulin.
C. Estimationofsubcutaneousinsulinrequirements
1. Multiplythefinalinsulininfusionratetimes24hours.Two-thirdsofthe
totaldoseisgiveninthemorningastwo-thirdsNPHandone-third
regular insulin. The remaining one-third of the total dose is given
beforesupperasone-halfNPHandone-halfregularinsulin.
2. Subsequentdosesshouldbeadjustedaccordingtothepatient'sblood
glucoseresponse.
AcuteRenalFailure
Acuterenalfailureisdefinedasasuddendecreaseinrenalfunctionsufficient
toincreasetheconcentrationofnitrogenouswastesintheblood.Itischaracter-
izedbyanincreasingBUNandcreatinine.
I. Clinicalpresentationofacuterenalfailure
A. Oliguriaisacommonindicatorofacuterenalfailure,anditismarkedby
adecreaseinurineoutputtolessthan30mL/h.Acuterenalfailuremaybe
oliguric(<500L/day)ornonoliguric(>30mL/h).Anuria(<100mL/day)does
notusuallyoccurinrenalfailure,anditspresencesuggestsobstructionor
avascularcause.
B.Acute renal failure may also be manifest by encephalopathy, volume
overload, pericarditis, bleeding, anemia, hyperkalemia, hyperphos-
phatemia,hypocalcemia,andmetabolicacidemia.
II. Clinicalcausesofrenalfailure
A. Prerenalinsult
1. Prerenal insult is the most common cause of acute renal failure,
accounting for 70% of cases. Prerenal failure is usually caused by
AcuteRenalFailure131
reducedrenalperfusionsecondarytoextracellularfluidloss(diarrhea,
diuresis,GIhemorrhage)orsecondarytoextracellularfluidsequestra-
tion (pancreatitis, sepsis), inadequate cardiac output, renal
vasoconstriction (sepsis, liver disease, drugs), or inadequate fluid
intakeorreplacement.
2. Mostpatientswithprerenalazotemiahaveoliguria,ahistoryoflarge
fluidlosses(vomiting,diarrhea,burns),andevidenceofintravascular
volumedepletion(thirst,weightloss,orthostatichypotension,tachycar-
dia,flatneckveins,drymucousmembranes).Patientswithcongestive
heartfailuremayhavetotalbodyvolume excess(distendedneck veins,
pulmonary and pedal edema) but still have compromised renal
perfusionandprerenalazotemiabecauseofdiminishedcardiacoutput.
3. Causes of prerenal failure are usually reversible if recognized and
treated early; otherwise, prolonged renal hypoperfusion can lead to
acutetubularnecrosisandpermanentrenalinsufficiency.
B.Intrarenalinsult
1. Acute tubular necrosis (ATN) is the most common intrinsic renal
diseaseleadingtoARF.
a. Prolonged renal hypoperfusion is the most common cause of
ATN.
b. Nephrotoxicagents(aminoglycosides, heavymetals,radiocontrast
media, ethylene glycol) represent exogenous nephrotoxins. ATN
may also occur as a result of endogenous nephrotoxins, such as
intratubular pigments (hemoglobinuria), intratubular proteins
(myeloma),andintratubularcrystals(uricacid).
2. Acuteinterstitialnephritis(AIN)isanallergicreactionsecondaryto
drugs(NSAIDs,$-lactams).
3. Arteriolar injury occurs secondary to hypertension, vasculitis,
microangiopathicdisorders.
4. Glomerulonephritissecondarytoimmunologicallymediatedinflamma-
tionmaycauseintrarenaldamage.
C. Postrenalinsultresultsfromobstructionofurineflow.Postrenalinsultis
the least common cause of acute renal failure, accounting for 10%.
Postrenal insult may be caused by obstruction secondary to prostate
cancer,benignprostatichypertrophy,orrenalcalculi.Postrenalinsultmay
be caused by amyloidosis, uric acid crystals, multiple myeloma,
methotrexate,oracyclovir.
III. Clinicalevaluationofacuterenalfailure
A. Initialevaluationofrenalfailureshoulddeterminewhetherthecauseis
decreasedrenalperfusion,obstructedurineflow,ordisordersoftherenal
parenchyma.Volume status(orthostaticpulse,bloodpressure,fluidintake
and output, daily weights, hemodynamic parameters), nephrotoxic
medications,andpatternofurineoutputshouldbeassessed.
B.Prerenal azotemia is likely when there is a history of heart failure or
extracellularfluidvolumelossordepletion.
C.Postrenalazotemiaissuggestedbyahistoryofdecreasedsizeorforce
oftheurinestream,anuria,flank pain,hematuria orpyuria,orcancerofthe
bladder,prostateorpelvis.
D.Intrarenalinsultissuggestedbyahistoryofprolongedvolumedepletion
(often post-surgical), pigmenturia, hemolysis, rhabdomyolysis, or
nephrotoxins. Intrarenal insult is suggested by recent radiocontrast,
132AcuteRenalFailure
aminoglycosideuse,orvascularcatheterization.Interstitialnephritismay
beimplicatedbyahistoryofmedicationrash,fever,orarthralgias.
E. Chronicrenalfailureissuggestedbydiabetesmellitus,normochromic
normocyticanemia,hypercalcemia,andhyperphosphatemia.
IV. Physicalexamination
A. Cardiacoutput,volumestatus,bladdersize,andsystemicdiseasemani-
festationsshouldbeassessed.
B.Prerenalazotemiaissuggestedbyimpairedcardiacoutput(neckvein
distention,pulmonaryrales,pedaledema).Volumedepletionis suggested
byorthostatic bloodpressurechanges,weightloss,lowurineoutput,or
diureticuse.
C.Flank,suprapubic,orabdominalmassesmayindicateanobstructive
cause.
D.Skinrashsuggestsdrug-inducedinterstitialnephritis;palpablepurpura
suggests vasculitis; nonpalpable purpura suggests thrombotic
thrombocytopenicpurpuraorhemolytic-uremicsyndrome.
E. Bladder catheterization is useful to rule out suspected bladder outlet
obstruction. A residual volume of more than 100 mL suggests bladder
outletobstruction.
F. Centralvenousmonitoringisusedtomeasurecardiacoutputandleft
ventricularfillingpressureifprerenalfailureissuspected.
V.Laboratoryevaluation
A. Spoturinesodiumconcentration
1. Spoturinesodiumcanhelpdistinguishbetweenprerenalazotemiaand
acutetubularnecrosis.
2. Prerenalfailurecausesincreasedreabsorptionofsaltandwaterand
willmanifestasalowspoturinesodiumconcentration<20mEq/Land
alowfractionalsodiumexcretion<1%,andaurine/plasmacreatinine
ration of >40. Fractional excretion of sodium (%) = ([urine so-
dium/plasmasodium][urinecreatinine/plasmacreatinine]x100).
3. Iftubularnecrosisisthecause,thespoturineconcentrationwillbe>40
mEq/L,andfractionalexcretionofsodiumwillbe>1%.
B.Urinalysis
1. Normalurinesedimentisastrongindicatorofprerenalazotemiaor
maybeanindicatorofobstructiveuropathy.
2. Hematuria, pyuria, or crystals may be associated with postrenal
obstructiveazotemia.
3. Abundantcells,casts,orproteinsuggestsanintrarenaldisorder.
4. Red cells alone may indicate vascular disorders. RBC casts and
abundantproteinsuggestglomerulardisease(glomerulonephritis).
5. Whitecellcastsandeosinophiliccastsindicateinterstitialnephritis.
6. Renal epithelial cell casts and pigmented granular casts are
associatedwithacutetubularnecrosis.
C.Ultrasound is useful for evaluation of suspected postrenal obstruction
(nephrolithiasis).Thepresenceofsmall(<10cminlength),scarredkid-
neysisdiagnosticofchronicrenalinsufficiency.
VI. Managementofacuterenalfailure
A. Reversible disorders, such as obstruction, should be excluded, and
hypovolemiashouldbecorrectedwithvolumereplacement.Cardiacoutput
shouldbemaintained.Incriticallyillpatients,apulmonaryarterycatheter
shouldbeusedforevaluationandmonitoring.
Hyperkalemia133
B.Extracellularfluidvolumeexpansion.Infusionofa1-2litercrystalloid
fluidbolusmayconfirmsuspectedvolumedepletion.
C.If the patient remains oliguric despite euvolemia, IV diuretics may be
administered. A large single dose of furosemide (100-200 mg) may be
administered intravenously to promote diuresis. If urine flow is not
improved,thedoseoffurosemidemaybedoubled.Furosemidemaybe
repeatedin2hours,oracontinuousIVinfusionof10-40mg/hr(max1000
mg/day)maybeused.
D.The dosage or dosing intervals of renally excreted drugs should be
modified.
E. Hyperkalemia is the most immediately life-threatening complication of
renalfailure.Serumpotassiumvaluesgreaterthan6.5mEq/Lmayleadto
arrhythmias and cardiac arrest. Potassium should be removed from IV
solutions.Hyperkalemiamaybetreatedwithsodiumpolystyrenesulfonate
(Kayexalate),30-60gmPO/PRevery4-6hours.
F. Hyperphosphatemiacanbecontrolledwithaluminumhydroxideantacids
(eg, Amphojel or Basaljel), 15-30 ml or one to three capsules PO with
meals,shouldbeused.
G. Fluids. After normal volume has been restored, fluid intake should be
reducedtoanamountequaltourinaryandotherlossesplusinsensible
lossesof300-500mL/day.Inoliguricpatients,dailyfluidintakemayneed
toberestrictedtolessthan1L.
H. Nutritional therapy. A renal diet consisting of daily high biologic value
proteinintakeof0.5gm/kg/d,sodium2g,potassium40-60mg/day,and
atleast35kcal/kgofnonproteincaloriesisrecommended.Phosphorus
shouldberestrictedto800mg/day
I. Dialysis. Indications for dialysis include uremic pericarditis, severe
hyperkalemia,pulmonaryedema,persistentseveremetabolicacidosis(pH
lessthan7.2),andsymptomaticuremia.
Hyperkalemia
Bodypotassiumis98%intracellular.Only2%oftotalbodypotassium,about70
mEq,isintheextracellularfluid,withthenormalconcentrationof3.5-5mEq/L.
I. Pathophysiologyofpotassiumhomeostasis
A. ThenormalupperlimitofplasmaKis5-5.5mEq/L,withameanKlevel
of4.3.
B. Externalpotassiumbalance.NormaldietaryKintakeis1-1.5mEq/kg
intheformofvegetablesandmeats.Thekidneyistheprimaryorganfor
preservingexternalKbalance,excreting90%ofthedailyKburden.
C. Internalpotassiumbalance.Potassiumtransfertoandfromtissues,is
affected by insulin, acid-base status, catecholamines, aldosterone,
plasmaosmolality,cellularnecrosis,andglucagon.
II. Clinicaldisordersofexternalpotassiumbalance
A. Chronicrenalfailure.Thekidneyisabletoexcretethedietaryintakeof
potassiumuntiltheglomerularfiltrationratefallsbelow10cc/minuteor
untilurineoutputfallsbelow1L/day.Renalfailureisadvancedbefore
hyperkalemiaoccurs.
134Hyperkalemia
B. Impaired renal tubular function. Renal diseases may cause
hyperkalemia,andtherenaltubularacidosiscausedbytheseconditions
mayworsenhyperkalemia.
C. Primaryadrenalinsufficiency(Addison'sdisease)isnowararecause
of hyperkalemia. Diagnosis is indicated by the combination of
hyperkalemiaandhyponatremiaandisconfirmedbyalowaldosterone
and a low plasma cortisol level that does not respond to adreno-
corticotropichormonetreatment.
D. Drugsthatmaycausehyperkalemiaincludenonsteroidalanti-inflamma-
torydrugs,angiotensin-convertingenzymeinhibitors,cyclosporine,and
potassium-sparingdiuretics.Hyperkalemiaisespeciallycommonwhen
thesedrugsaregiventopatientsatriskforhyperkalemia(diabetics,renal
failure,advancedage).
E. Excessivepotassiumintake
1. Long-termpotassiumsupplementationresultsinhyperkalemiamost
oftenwhenanunderlyingimpairmentinrenalexcretionalreadyexists.
2. Intravenousadministrationof0.5mEq/kgover1hourincreasesserum
levels by 0.6 mEq/L. Hyperkalemia often results when infusions of
greaterthan40mEq/houraregiven.
III. Clinicaldisordersofinternalpotassiumbalance
A. Diabeticpatientsareatparticularriskforseverehyperkalemiabecause
ofrenalinsufficiencyandhyporeninemichypoaldosteronism.
B. Systemic acidosis reduces renal excretion of potassium and moves
potassiumoutofcells,resultinginhyperkalemia.
C. Endogenous potassium release from muscle injury, tumor lysis, or
chemotherapymayelevateserumpotassium.
IV. Manifestationsofhyperkalemia
A. Hyperkalemia, unless severe, is usually asymptomatic. The effect of
hyperkalemiaontheheartbecomessignificantabove6mEq/L.Aslevels
increase,theinitialECGchangeistallpeakedTwaves.TheQTinterval
isnormalordiminished.
B. AsKlevelsrisefurther,thePRintervalbecomesprolonged,thentheP
waveamplitudedecreases.TheQRScomplexeventuallywidensintoa
sinewavepattern,withsubsequentcardiacstandstill.
C. At serum K is >7 mEq/L, muscle weakness may lead to a flaccid
paralysis.Sensoryabnormalities,impairedspeechandrespiratoryarrest
mayfollow.
V. Pseudohyperkalemia
A. Potassium may be falsely elevated by hemolysis during phlebotomy,
when K is released from ischemic muscle distal to a tourniquet, and
becauseoferythrocytefragilitydisorders.
B. Falselyhighlaboratorymeasurementofserumpotassiummayoccurwith
markedlyelevatedplateletcounts(>10
6
platelet/mm
3
)orwhitebloodcell
counts(>50,000/mm
3
).
VI. Diagnosticapproachtohyperkalemia
A. TheserumKlevelshouldberepeattestedtoruleoutlaboratoryerror.If
significantthrombocytosisorleukocytosisispresent,aplasmapotassium
levelshouldbedetermined.
B. The24-hoururineoutput,urinaryKexcretion,bloodureanitrogen,and
serumcreatinineshouldbemeasured.Renal K retentionisdiagnosed
whenurinaryKexcretionislessthan20mEq/day.
Hyperkalemia135
C. HighurinaryK,excretionof>20mEq/day,isindicativeof excessiveK
intakeasthecause.
VII. Renalhyperkalemia
A. IfurinaryKexcretionislowandurineoutputisintheoliguricrange,and
creatinine clearance is lower than 20 cc/minute, renal failure is the
probablecause.Prerenalazotemiaresultingfromvolumedepletionmust
beruledoutbecausethehyperkalemiawillrespondtovolumerestoration.
B. WhenurinaryKexcretionislow,yetbloodureanitrogenandcreatinine
levelsarenotelevatedandurinevolumeisatleast1Ldailyandrenal
sodiumexcretionisadequate(about20mEq/day),theneitheradefectin
thesecretionofreninoraldosteroneortubularresistancetoaldosterone
is likely. Low plasma renin and aldosterone levels, will confirm the
diagnosis of hyporeninemic hypoaldosteronism. Addison's disease is
suggestedbyalowserumcortisol,andthediagnosisisconfirmedwitha
ACTH(Cortrosyn)stimulationtest.
C. When inadequate K excretion is not caused by hypoaldosteronism, a
tubulardefectinKclearanceissuggested.Urinarytractobstruction,renal
transplant,lupus,oramedicationshouldbeconsidered.
VIII. Extrarenalhyperkalemia
A. WhenhyperkalemiaoccursalongwithhighurinaryKexcretionof>20
mEq/day, excessive intake of K is the cause. Potassium excess in IV
fluids,diet,ormedicationshouldbesought.Aconcomitantunderlying
renaldefectinKexcretionisalsolikelytobepresent.
B. Bloodsugarshouldbemeasuredtoruleoutinsulindeficiency;bloodpH
andserumbicarbonateshouldbemeasuredtoruleoutacidosis.
C. Endogenous sources of K, such as tissue necrosis, hypercatabolism,
hematoma,gastrointestinalbleeding,orintravascularhemolysisshould
beexcluded.
IX. Managementofhyperkalemia
A. Acutetreatmentofhyperkalemia
1. Calcium
a. IftheelectrocardiogramshowslossofPwavesorwideningofQRS
complexes,calciumshouldbegivenIV;calciumreducesthecell
membranethresholdpotential.
b. Calciumchloride(10%)2-3gshouldbegivenover5minutes.In
patients with circulatory compromise, 1 g of calcium chloride IV
shouldbegivenover3minutes.
c. Iftheserum K level isgreaterthan7mEq/L,calciumshouldbe
given.Ifdigitalisintoxicationissuspected,calciummustbegiven
cautiously. Coexisting hyponatremia should be treated with
hypertonicsaline.
2. Insulin:IftheonlyECGabnormalitiesarepeakedTwavesandthe
serum level is under 7 mEq/L, treatment should begin with insulin
(regularinsulin,5-10UbyIVpush)with50%dextrosewater(D50W)
50mLIVpush.Repeatedinsulindosesof10Uandglucosecanbe
givenevery15minutesformaximaleffect.
3. SodiumbicarbonatepromotescellularuptakeofK.Itshouldbegiven
as1-2vials(50-mEq/vials) IVpush.
4. Potassiumeliminationmeasures
a. Sodiumpolystyrenesulfonate(Kayexalate)isacationexchange
resinwhichbindstopotassiuminthelowerGItract.Dosageis30-
60gmpremixedwithsorbitol20%PO/PR.
136Hypokalemia
b. Furosemide (Lasix) 100 mg IV should be given to promote
kaliuresis.
c. Emergenthemodialysisforhyperkalemiaisrarelynecessaryexcept
whenrefractorymetabolicacidosisispresent.
Hypokalemia
Hypokalemiaischaracterizedbyaserumpotassiumconcentrationoflessthan
3.5mEq/L.Ninety-eightpercentofKisintracellular.
I. Pathophysiologyofhypokalemia
A. Cellularredistributionofpotassium.Hypokalemiamayresultfromthe
intracellular shift of potassium by insulin, beta-2 agonist drugs, stress
induced catecholamine release, thyrotoxic periodic paralysis, and
alkalosis-inducedshift(metabolicorrespiratory).
B. Nonrenalpotassiumloss
1. Gastrointestinal loss can be caused by diarrhea, laxative abuse,
villous adenoma, biliary drainage, enteric fistula, clay ingestion,
potassiumbindingresiningestion,ornasogastricsuction.
2. Sweating,prolongedlow-potassiumdiet,hemodialysisandperitoneal
dialysismayalsocausenonrenalpotassiumloss.
C. Renalpotassiumloss
1. Hypertensivehighreninstates.Malignanthypertension,renal artery
stenosis,renin-producingtumors.
2. Hypertensive low renin, high aldosterone states. Primary
hyperaldosteronism(adenomaorhyperplasia).
3. Hypertensivelowrenin,lowaldosteronestates.Congenitaladrenal
hyperplasia(11or17hydroxylasedeficiency),Cushing'ssyndromeor
disease, exogenous mineralocorticoids (Florinef, licorice, chewing
tobacco),Liddle'ssyndrome.
4. Normotensivestates
a. Metabolicacidosis.Renaltubularacidosis(typeIorII)
b. Metabolicalkalosis(urinechloride<10mEq/day).Vomiting
c. Metabolic alkalosis (urine chloride >10 mEq/day). Bartter's
syndrome,diuretics,magnesiumdepletion,normotensivehyper-
aldosteronism
5. Drugs associated with potassium loss include amphotericin B,
ticarcillin,piperacillin,andloopdiuretics.
II. Clinicaleffectsofhypokalemia
A. Cardiaceffects.Themostlethalconsequenceofhypokalemiaiscardiac
arrhythmia. Electrocardiographic effects include a depressed ST seg-
ment, decreased T-wave amplitude, U waves, and a prolonged QT-U
interval.
B. Musculoskeletal effects. The initial manifestation of K depletion is
muscle weakness, which can lead to paralysis. In severe cases,
respiratorymuscleparalysismayoccur.
C. Gastrointestinaleffects.Nausea,vomiting,constipation,andparalytic
ileusmaydevelop.
III.Diagnosticevaluation
Hypermagnesemia137
A. The 24-hour urinary potassium excretion should be measured. If >20
mEq/day, excessive urinary K loss is the cause. If <20 mEq/d, low K
intake,ornon-urinaryKlossisthecause.
B. InpatientswithexcessiverenalKlossandhypertension,plasmarenin
andaldosteroneshouldbemeasuredtodifferentiateadrenalfromnon-
adrenalcausesofhyperaldosteronism.
C. IfhypertensionisabsentandserumpHisacidotic,renaltubularacidosis
shouldbeconsidered.IfhypertensionisabsentandserumpHisnormal
to alkalotic, a high urine chloride (>10 mEq/d) suggests hypokalemia
secondarytodiureticsorBartter'ssyndrome.Alowurinechloride(<10
mEq/d)suggestsvomiting.
IV. Emergencytreatmentofhypokalemia
A. Indicationsforurgentreplacement.Electrocardiographicabnormalities,
myocardial infarction, hypoxia, digitalis intoxication, marked muscle
weakness,orrespiratorymuscleparalysis.
B. Intravenouspotassiumtherapy
1. Intravenous KCL is usually used unless concomitant hypo-
phosphatemiaispresent,wherepotassiumphosphateisindicated.
2. ThemaximalrateofintravenousKreplacementis30mEq/hour.The
KconcentrationofIVfluidsshouldbe80mEq/Lorlessifgivenviaa
peripheral vein. Frequent monitoring of serum K and constant
electrocardiographic monitoring is recommended when potassium
levelsarebeingreplaced.
V. Non-emergenttreatmentofhypokalemia
A. AttemptsshouldbemadetonormalizeKlevelsif<3.5mEq/L.
B. Oralsupplementationis significantlysaferthanIV.Liquidformulationsare
preferred due to rapid oral absorption, compared to sustained release
formulations,whichareabsorbedoverseveralhours.
1. KCLelixir20-40mEqqd-tidPOaftermeals.
2. Micro-K,10mEqtabs,2-3tabstidPOaftermeals(40-100mEq/d).
Hypomagnesemia
Magnesiumdeficiencyoccursinupto11%ofhospitalizedpatients.Thenormal
rangeofserum magnesiumis1.5to2.0 mEq/L,whichismaintainedbythe
kidney,intestine,andbone.
I. Pathophysiology
A. Decreasedmagnesiumintake.Protein-caloriemalnutrition,prolonged
parenteralfluidadministration,andcatabolicillnessarecommoncauses
ofhypomagnesemia.
B. Gastrointestinal losses of magnesium may result from prolonged
nasogastricsuction,laxativeabuse,andpancreatitis.
C. Renallossesofmagnesium
1. Renal loss of magnesium may occur secondary to renal tubular
acidosis, glomerulonephritis, interstitial nephritis, or acute tubular
necrosis.
2. Hyperthyroidism,hypercalcemia,andhypophosphatemiamaycause
magnesiumloss.
138Hypermagnesemia
3. Agentsthatenhancerenalmagnesiumexcretionincludealcohol,
loopandthiazidediuretics,amphotericinB,aminoglycosides,cisplatin,
andpentamidine.
D. Alterationsinmagnesiumdistribution
1. Redistribution of circulating magnesium occurs by extracellular to
intracellularshifts,sequestration,hungrybonesyndrome,orbyacute
administrationofglucose,insulin,oraminoacids.
2. Magnesiumdepletioncanbecausedbylargequantitiesofparenteral
fluidsandpancreatitis-inducedsequestrationofmagnesium.
II. Clinicalmanifestationsofhypomagnesemia
A. NeuromuscularfindingsmayincludepositiveChvostek'sandTrous-
seau'ssigns,tremors,myoclonicjerks,seizures,andcoma.
B. Cardiovascular. Ventricular tachycardia, ventricular fibrillation, atrial
fibrillation,multifocalatrialtachycardia,ventricularectopicbeats,hyper-
tension, enhancement of digoxin-induced dysrhythmias, and cardio-
myopathies.
C. ECGchangesincludeventriculararrhythmias(extrasystoles,tachycardia)
and atrial arrhythmias (atrial fibrillation, supraventricular tachycardia,
torsades de Pointes). Prolonged PR and QT intervals, ST segment
depression,T-waveinversions,wideQRScomplexes,andtallT-waves
mayoccur.
III.Clinicalevaluation
A. Hypomagnesemiaisdiagnosedwhentheserummagnesiumislessthan
0.7-0.8 mmol/L. Symptoms of magnesium deficiency occur when the
serummagnesiumconcentrationislessthan0.5mmol/L.A24-hoururine
collection for magnesium is the first step in the evaluation of
hypomagnesemia.Hypomagnesiacausedbyrenalmagnesiumlossis
associatedwithmagnesiumexcretionthatexceeds24mg/day.
B. Lowurinarymagnesiumexcretion(<1mmol/day),withconcomitantserum
hypomagnesemia, suggests magnesium deficiency due to decreased
intake,nonrenallosses,orredistributionofmagnesium.
IV. Treatmentofhypomagnesemia
A. Asymptomaticmagnesiumdeficiency
1. In hospitalized patients, the daily magnesium requirements can be
providedthrougheitherabalanceddiet,asoralmagnesiumsupple-
ments (0.36-0.46 mEq/kg/day), or 16-30 mEq/day in a parenteral
nutritionformulation.
2. Magnesiumoxideisbetterabsorbedandlesslikelytocausediarrhea
thanmagnesiumsulfate.MagnesiumoxidepreparationsincludeMag-
Ox400(240mgelementalmagnesiumper400mgtablet),Uro-Mag
(84mgelementalmagnesiumper400 mg tablet),andmagnesium
chloride(Slo-Mag)64mg/tab,1-2tabsbid.
B. Symptomaticmagnesiumdeficiency
1. Serummagnesium#0.5mmol/LrequiresIVmagnesiumrepletionwith
electrocardiographicandrespiratorymonitoring.
2. Magnesiumsulfate1-6gmin500mLofD5WcanbeinfusedIVat1
gm/hr.Anadditional6-9gmofMgSO
4
shouldbegivenbycontinuous
infusionoverthenext24hours.
Hypermagnesemia139
Hypermagnesemia
Serum magnesium has a normal range of 0.8-1.2 mmol/L. Magnesium
homeostasis is regulated by renal and gastrointestinal mechanisms.
Hypermagnesemiaisusuallyiatrogenicandisfrequentlyseeninconjunctionwith
renalinsufficiency.
I. Clinicalevaluationofhypermagnesemia
A. Causesofhypermagnesemia
1. Renal.Creatinineclearance<30mL/minute.
2. Nonrenal. Excessive use of magnesium cathartics, especially with
renalfailure;iatrogenicovertreatmentwithmagnesiumsulfate.
B. Cardiovascularmanifestationsofhypermagnesemia
1. Hypermagnesemia<10mEq/L.Delayedinterventricularconduction,
first-degreeheartblock,prolongationoftheQ-Tinterval.
2. Levelsgreaterthan10mEq/L.Low-gradeheartblockprogressing
to complete heart block and asystole occurs at levels greater than
12.5mmol/L(>6.25mmol/L).
C. Neuromusculareffects
1. Hyporeflexia occurs at a magnesium level >4 mEq/L (>2 mmol/L);
diminution of deep tendon reflexes is an early sign of magnesium
toxicity.
2. Respiratorydepressionduetorespiratorymuscleparalysis,somno-
lenceandcomaoccuratlevels>13mEq/L(6.5mmol/L).
3. Hypermagnesemia should always be considered when these
symptoms occur in patients with renal failure, in those receiving
therapeuticmagnesium,andinlaxativeabuse.
II. Treatmentofhypermagnesemia
A. Asymptomatic, hemodynamically stable patients. Moderate hyper-
magnesemiacanbemanagedbyeliminationofintake.
B. Severehypermagnesemia
1. Furosemide20-40mgIVq3-4hshouldbegivenasneeded.Saline
diuresisshouldbeinitiatedwith0.9% saline,infusedat120cc/hto
replaceurineloss.
2. IfECGabnormalities(peakedTwaves,lossofPwaves,orwidened
QRScomplexes)orifrespiratorydepressionispresent,IVcalcium
gluconateshouldbegivenas1-3ampules(10%solution,1gmper10
mLamp),addedtosalineinfusate.Calciumgluconatecanbeinfused
to reverse acute cardiovascular toxicity or respiratory failure as 15
mg/kgovera4-hourperiod.
3. Parenteralinsulinandglucosecanbegiventoshiftmagnesiuminto
cells. Dialysis is necessary for patients who have severe
hypermagnesemia.
140DisordersofWaterandSodiumBalance
DisordersofWaterandSodiumBalance
I. Pathophysiologyofwaterandsodiumbalance
A. Volitional intake of water is regulated by thirst. Maintenance intake of
wateristheamountofwatersufficienttooffsetobligatorylosses.
B. Maintenancewaterneeds
= 100mL/kgforfirst10kgofbodyweight
+ 50mL/kgfornext10kg
+ 20mL/kgforweightgreaterthan20kg
C. Clinicalsignsofhyponatremia.Confusion,agitation,lethargy,seizures,
andcoma.
D. Pseudohyponatremia
1. Elevationofbloodglucosemaycreatesanosmoticgradientthatpulls
waterfrom cellsintotheextracellularfluid,dilutingtheextracellular
sodium.Thecontributionofhyperglycemiatohyponatremiacanbe
estimatedusingthefollowingformula:
Expectedchangeinserumsodium=(serumglucose-100)x0.016
2. Marked elevation of plasma lipids or protein can also result in
erroneous hyponatremia because of laboratory inaccuracy. The
percentage of plasma water can be estimated with the following
formula:
%plasmawater=100-[0.01xlipids(mg/dL)]-[0.73xprotein(g/dL)]
II. Diagnosticevaluationofhyponatremia
A. Pseudohyponatremiashouldbeexcludedbyrepeattesting.Thecauseof
thehyponatremiashouldbedeterminedbasedonhistory,physicalexam,
urine osmolality, serum osmolality, urine sodium and chloride. An
assessmentofvolumestatusshoulddetermineifthepatientisvolume
contracted,normalvolume,orvolumeexpanded.
B. Classificationofhyponatremicpatientsbasedonurineosmolality
1. Low-urineosmolality(50-180mOsm/L)indicatesprimaryexcessive
waterintake(psychogenicwaterdrinking).
2. High-urineosmolality(urineosmolality>serumosmolality)
a. High-urine sodium (>40 mEq/L) and volume contraction
indicatesarenalsourceofsodiumlossandfluidloss(excessive
diureticuse,salt-wastingnephropathy,Addison'sdisease,osmotic
diuresis).
b. High-urine sodium (>40 mEq/L) and normal volumeis most
likely caused by water retention due to a drug effect,
hypothyroidism, or the syndrome of inappropriate antidiuretic
hormone secretion. In SIADH, the urine sodium level is usually
high.SIADH isfoundinthepresenceofamalignanttumorora
disorderofthepulmonaryorcentralnervoussystem.
c. Low-urinesodium(<20mEq/L)andvolumecontraction,dry
mucous membranes, decreased skin turgor, and orthostatic
hypotensionindicateanextrarenalsourceoffluidloss(gastrointes-
tinaldisease,burns).
d. Low-urine sodium (<20 mEq/L) and volume-expansion, and
edemaiscausedbycongestiveheartfailure,cirrhosiswithascites,
or nephrotic syndrome. Effective arterial blood volume is de-
creased.Decreasedrenalperfusioncausesincreasedreabsorp-
tionofwater.
DisordersofWaterandSodiumBalance141
DrugsAssociatedwithSIADH
Acetaminophen
Barbiturates
Carbamazepine
Chlorpropamide
Clofibrate
Cyclophosphamide
Indomethacin
Isoproterenol
ProstaglandinE
1
Meperidine
Nicotine
Tolbutamide
Vincristine
III.Treatmentofwaterexcesshyponatremia
A. Determinethevolumeofwaterexcess
Waterexcess=totalbodywaterx([140/measuredsodium]-1)
B. Treatment of asymptomatic hyponatremia. Water intake should be
restricted to 1,000 mL/day. Food alone in the diet contains this much
water,so noliquidsshouldbeconsumed.Ifanintravenoussolutionis
needed, an isotonic solution of 0.9% sodium chloride (normal saline)
shouldbeused.Dextroseshouldnotbeusedintheinfusionbecausethe
dextroseismetabolizedintowater.
C. Treatmentofsymptomatichyponatremia
1. If neurologic symptoms of hyponatremia are present, the serum
sodiumlevelshouldbecorrectedwithhypertonicsaline.Excessively
rapidcorrectionofsodiummayresultinasyndromeofcentralpontine
demyelination.
2. Theserumsodiumshouldberaisedatarateof1mEq/Lperhour.If
hyponatremia has been chronic, the rate should be limited to 0.5
mEq/Lperhour.Thegoalofinitialtherapyisaserumsodiumof125-
130mEq/L,thenwaterrestrictionshouldbecontinueduntilthelevel
normalizes.
3. The amount of hypertonic saline needed is estimated using the
followingformula:
Sodiumneeded(mEq)=0.6xwtinkgx(desiredsodium-measured
sodium)
4. Hypertonic3%sodiumchloridecontains513mEq/Lofsodium.The
calculatedvolumerequiredshouldbeadministeredovertheperiod
requiredtoraisetheserumsodiumlevelatarateof0.5-1mEq/Lper
hour.Concomitantadministrationoffurosemidemayberequiredto
lessentheriskoffluidoverload.
IV. Hypernatremia
A. Clinical manifestations of hypernatremia: Clinical manifestations
include tremulousness, irritability, ataxia, spasticity, mental confusion,
seizures,andcoma.
B. Causesofhypernatremia
1. Netsodiumgainornetwaterlosswillcausehypernatremia
2. Failuretoreplaceobligatewaterlossesmaycausehypernatremia,as
inpatientsunabletoobtainwaterbecauseofanalteredmentalstatus
orseveredebilitatingdisease.
3. Diabetesinsipidus:If urinevolumeishighbuturineosmolalityislow,
diabetesinsipidusisthemostlikelycause.
142DisordersofWaterandSodiumBalance
DrugsAssociatedwithDiabetesInsipidus
Ethanol
Phenytoin
Chlorpromazine
Lithium
Demeclocycline
Tolazamide
Glyburide
AmphotericinB
Colchicine
Vinblastine
C. Diagnosisofhypernatremia
1. Assessment of urine volume and osmolality are essential in the
evaluation of hyperosmolality. The usual renal response to
hypernatremiaistheexcretionoftheminimumvolume(#500mL/day)
of maximally concentrated urine (urine osmolality >800 mOsm/kg).
Thesefindingssuggestextrarenalwaterloss.
2. Diabetes insipidus generally presents with polyuria and hypotonic
urine(urineosmolality<250mOsm/kg).
V. Managementofhypernatremia
A. If there is evidence of hemodynamic compromise (eg, orthostatic
hypotension,markedoliguria),fluiddeficitsshouldbecorrectedinitially
with isotonic saline. Once hemodynamic stability is achieved, the
remainingfreewaterdeficitshouldbecorrectedwith5%dextrosewater
or0.45%NaCl.
B. Thewaterdeficitcanbeestimatedusingthefollowingformula:
Waterdeficit=0.6xwtinkgx(1-[140/measuredsodium]).
C. Thechangeinsodiumconcentrationshouldnotexceed1mEq/liter/hour.
One-halfofthecalculatedwaterdeficitcanbeadministeredinthefirst24
hours,followedbycorrectionoftheremainingdeficitoverthenext1-2
days.TheserumsodiumconcentrationandECFvolumestatusshouldbe
evaluatedevery6hours.Excessivelyrapidcorrectionofhypernatremia
mayleadtolethargyandseizuressecondarytocerebraledema.
D. Maintenancefluidneedsfromongoingrenalandinsensiblelossesmust
also be provided. If the patient is conscious and able to drink, water
shouldbegivenorallyorbynasogastrictube.
E. Treatmentofdiabetesinsipidus
1. Vasopressin(Pitressin)5-10UIV/SQq6h;fastonsetofactionwith
shortduration.
2. Desmopressin(DDAVP)2-4mcgIV/SQq12h;slowonsetofaction
withlongdurationofeffect.
VI. Mixeddisorders
A. Water excess and saline deficit occurs when severe vomiting and
diarrhea occur in a patient who is given only water. Clinical signs of
volumecontractionandalowserumsodiumarepresent.Salinedeficitis
replacedandfreewaterintakerestricteduntiltheserumsodiumlevelhas
normalized.
B. Waterandsalineexcessoftenoccurswithheartfailure,manifestingas
edemaandalow serum sodium.Anincreaseintheextracellularfluid
volume,asevidencedbyedema,isasalineexcess.Amarkedexcessof
free water expands the extracellular fluid volume, causing apparent
hyponatremia. However, the important derangement in edema is an
excessofsodium.Sodiumandwaterrestrictionanduseoffurosemide
areusuallyindicatedinadditiontotreatmentoftheunderlyingdisorder.
HypercalcemicCrisis143
C. Waterandsalinedeficitisfrequentlycausedbyvomitingandhighfever
and is characterized by signs of volume contraction and an elevated
serumsodium.Salineandfreewatershouldbereplacedinadditionto
maintenanceamountsofwater.
HypercalcemicCrisis
Hypercalcemic crisis is defined as an elevation in serum calcium that is
associatedwithvolumedepletion,mentalstatuschanges,andlife-threatening
cardiac arrhythmias. Hypercalcemic crisis is most commonly caused by
malignancy-associatedboneresorption.
I. Diagnosis
A. Hypercalcemic crisis is often complicated by nausea, vomiting,
hypovolemia,mentalstatuschanges,andhypotension.
B. A correction for the low albumin level must be made because ionized
calciumisthephysiologicallyimportantformofcalcium.
Correctedserumcalcium(mg/dL)=serumcalcium+0.8x(4.0-albumin
[g/dL])
C. Most patients in hypercalcemic crisis have a corrected serum calcium
levelgreaterthan13mg/dL.
D. TheECGoftendemonstratesashortQTinterval.Bradyarrhythmias,heart
blocks,andcardiacarrestmayalsooccur.
II. Treatmentofhypercalcemiccrisis
A. Normalsalineshouldbeadministereduntilthepatientisnormovolemic.
Ifsignsoffluidoverloaddevelop,furosemide(Lasix)canbegiventopro-
mote sodium and calcium diuresis. Thiazide diuretics, vitamin D
supplements and antacids containing sodium bicarbonate should be
discontinued.
B. Pamidronate disodium (Aredia) is the agent of choice for long-term
treatmentofhypercalcemia.Asingledoseof 90-mginfusedIVover24
hoursshouldnormalizecalciumlevelsin4to7days.Thepamidronate
doseof30-to90-mgIVinfusionmayberepeated7daysaftertheinitial
dose.Smallerdoses(30or60mgIVover4hours)aregiveneveryfew
weekstomaintainnormalcalciumlevels.
C. Calcitonin(Calcimar,Miacalcin)hastheadvantageofdecreasingserum
calciumlevelswithinhours;4to8U/kgSQ/IMq12h.Calcitoninshouldbe
usedinconjunctionwithpamidronateinseverelyhypercalcemicpatients.
144Hypophosphatemia
Hypophosphatemia
Clinical manifestations of hypophosphatemia include heart failure, muscle
weakness,tremor,ataxia,seizures,coma,respiratoryfailure,delayedweaning
fromventilator,hemolysis,andrhabdomyolysis.
I. Differentialdiagnosisofhypophosphatemia
Hyperphosphatemia145
A. Increasedurinaryexcretion:Hyperparathyroidism,renaltubulardefects,
diuretics.
B. Decrease in GI absorption: Malnutrition, malabsorption, phosphate
bindingminerals(aluminum-containingantacids).
C. Abnormal vitamin D metabolism: Vitamin D deficiency, familial hypo-
phosphatemia,tumor-associatedhypercalcemia.
D. Intracellular shifts of phosphate: Diabetic ketoacidosis, respiratory
alkalosis,alcoholwithdrawal,recoveryphaseofstarvation.
II. Labs:Phosphate,SMA12,LDH,magnesium,calcium,albumin,PTH,urine
electrolytes.24-hrurinephosphate,andcreatinine.
III. Diagnosticapproachtohypophosphatemia
A. 24-hrurinephosphate
1. If 24-hour urine phosphate is less than 100 mg/day, the cause is
gastrointestinal losses (emesis, diarrhea, NG suction, phosphate
binders),vitaminDdeficit,refeeding,recoveryfromburns,alkalosis,
alcoholism,orDKA.
2. If24-hoururinephosphateisgreaterthan100mg/day,thecauseis
renallosses,hyperparathyroidism,hypomagnesemia,hypokalemia,
acidosis,diuresis,renaltubulardefects,orvitaminDdeficiency.
IV. Treatment
A. Mildhypophosphatemia(1.0-2.5mEq/dL)
1. NaorKphosphate0.25mMol/kgIVinfusionattherateof10mMol/hr
(inNSorD5W150-250mL),mayrepeatasneeded.
2. Neutral phosphate (Nutra-Phos), 2 packs PO bid-tid (250 mg
elementalphosphorus/pack.
B. Severehypophosphatemia(<1.0mEq/dL)
1. AdministerNaorKphosphate0.5mMoles/KgIVinfusionattherate
of10mMoles/hr(NSorD5W150-250mL),mayrepeatasneeded.
2. Add potassium phosphate to IV solution in place of KCl (max 80
mEq/L infused at 100-150 mL/h). Max IV dose 7.5 mg phospho-
rus/kg/6hOR2.5-5mgelementalphosphorus/kgIVover6h.Giveas
potassiumorsodiumphosphate(93mgphosphate/mLand4mEq
Na+orK+/mL).DonotmixcalciumandphosphorusinsameIV.
Hyperphosphatemia
I. Clinicalmanifestationsofhyperphosphatemia:Hypotension,bradycardia,
arrhythmias, bronchospasm, apnea, laryngeal spasm, tetany, seizures,
weakness,psychosis,confusion.
II. Clinicalevaluationofhyperphosphatemia
A. Exogenous phosphate administration: Enemas, laxatives, diphos-
phonates,vitaminDexcess.
B. Endocrine disturbances: Hypoparathyroidism, acromegaly, PTH
resistance.
C. Labs: Phosphate, SMA 12, calcium, parathyroid hormone. 24-hr urine
phosphate,creatinine.
146Hyperphosphatemia
III. Therapy:Correcthypocalcemia,restrictdietaryphosphate,salinediuresis.
A. Moderatehyperphosphatemia
1. Aluminum hydroxide (Amphojel) 5-10 mL or 1-2 tablets PO ac tid;
aluminum containing agents bind to intestinal phosphate, and
decreasesabsorptionOR
2. Aluminumcarbonate(Basaljel)5-10mLor1-2tabletsPOactidOR
3. Calciumcarbonate(Oscal)(250or500mgelementalcalcium/tab)1-2
gm elementalcalciumPOactid.Keepcalcium-phosphateproduct
<70;startonlyifphosphate<5.5.
B. Severehyperphosphatemia
1. Volumeexpansionwith0.9%saline1Lover1hifthepatientisnot
azotemic.
2. Dialysisisrecommendedforpatientswithrenalfailure.
References
Al-ShamadiSM,CameronEC,SuttonRA,AW.J.KidneyDis1994;24:737-52
DeMarchiS,CecchinE,BanileA,BertottiA:NEJM1993;329:1927-34
Berger W, Keller U: Treatment of diabetic ketoacidosis and non-ketotic hyperosmolar
diabeticcoma.BaillieresClinEndoandMetab,Jan,6(1):1,1992.
CommonlyUsedFormulas
A-agradient=[(P
B
-PH
2
O)FiO
2
-PCO
2
/R]-PO
2
arterial
=(713xFiO
2
-pCO
2
/0.8)-pO
2
arterial
P
B
=760mmHg; PH
2
O=47mmHg; R.0.8
normalAagradient<10-15mmHg(roomair)
ArterialO
2
content=1.36(Hgb)(SaO
2
)+0.003(PaO
2
)
O
2
delivery=COxarterialO
2
content
Cardiacoutput=HRxstrokevolume
NormalCO=4-6L/min
SVR= MAP-CVPx80=NL800-1200dyne/sec/cm
2
CO
L/min
PVR= PA-PCWPx80=NL45-120dyne/sec/cm
2
CO
L/min
Normalcreatinineclearance=100-125mL/min(males),85-105(females)
Bodywaterdeficit(L)= 0.6(weightkg)([measuredserumNa]-140)
140
OsmolalitymOsm/kg=2[Na+K]+ BUN + glucose=NL270-290 mOsm
2.8 18 kg
FractionalexcretedNa= UNa/SerumNax100=NL<1%
UCr/SerumCr
AnionGap=Na+K-(Cl+HCO
3
)
Foreach100mg/dL8inglucose,Na+9by1.6mEq/L.
Corrected =measuredCamg/dL+0.8x(4-albuming/dL)
serumCa
+
(mg/dL)
Basalenergyexpenditure(BEE):
Males=66+(13.7xactualweightKg)+(5xheightcm)-(6.8xage)
Females=655+(9.6xactualweightKg)+(1.7xheightcm)-(4.7xage)
NitrogenBalance=Gmproteinintake/6.25-urineureanitrogen-(3-4
gm/dinsensibleloss)
CommonlyUsedDrugLevels
Drug TherapeuticRange*
Amikacin . . . . . . . . . . . . . . Peak 25-30; trough<10mcg/mL
Amiodarone . . . . . . . . . . . 1.0-3.0 mcg/mL
Amitriptyline . . . . . . . . . . . 100-250ng/mL
Carbamazepine . . . . . . . . 4-10 mcg/mL
Chloramphenicol . . . . . . . Peak 10-15; trough<5mcg/mL
Desipramine . . . . . . . . . . . 150-300ng/mL
Digoxin . . . . . . . . . . . . . . . 0.8-2.0 ng/mL
Disopyramide . . . . . . . . . . 2-5 mcg/mL
Doxepin . . . . . . . . . . . . . . 75-200ng/mL
Flecainide . . . . . . . . . . . . . 0.2-1.0 mcg/mL
Gentamicin . . . . . . . . . . . . Peak 6.0-8.0; trough<2.0mcg/mL
Imipramine . . . . . . . . . . . . 150-300ng/mL
Lidocaine . . . . . . . . . . . . . 2-5 mcg/mL
Lithium . . . . . . . . . . . . . . . 0.5-1.4 mEq/L
Nortriptyline . . . . . . . . . . . 50-150ng/mL
Phenobarbital . . . . . . . . . . 10-30 mEq/mL
Phenytoin** . . . . . . . . . . . . 8-20 mcg/mL
Procainamide . . . . . . . . . . 4.0-8.0 mcg/mL
Quinidine . . . . . . . . . . . . . 2.5-5.0 mcg/mL
Salicylate . . . . . . . . . . . . . 15-25 mg/dL
Theophylline . . . . . . . . . . . 8-20 mcg/mL
Valproic acid . . . . . . . . . . . 50-100mcg/mL
Vancomycin . . . . . . . . . . . Peak 30-40; trough<10mcg/mL
*Thetherapeuticrangeofsomedrugsmayvarydependingonthereferencelab
used.
** Therapeutic range of phenytoin is 4-10 mcg/mL in presence of significant
azotemiaand/orhypoalbuminemia.
Index
Abacavir85
Abciximab31
Abelcet86
Accolate60
Accupril34
AcetaminophenOverdose106
Acetate19
ACLS5
Activase29,57,117
ActivatedCharcoal105
ActivatedproteinC89
Acutecoronarysyndromes25
Acutetubularnecrosis128
Acyclovir85
AdmissionCheckList16
AeroBid59,64
AeroBid-M64
Agenerase85
Aggrastat31
Aggrenox119
Albuterol59,63
Alcoholicketoacidosis125
Aldactone34
Altace34
Alteplase29,57
Aluminumcarbonate141
Aluminumhydroxide141
Alveolar/arterial O2 gradient
142
Amidate49
Amikacin82,90
Amikin90
Aminoacid19
Aminoacidsolution19
Aminocaproicacid74
Aminosyn19
Amiodarone40,41,45
Amoxicillin65
Amoxicillin/Clavulanate65,81
Amphojel141
AmphotericinB86
Amphotericin B lipid complex
86
Ampicillin/Sulbactam 82, 90,
91
Amprenavir85
Anectine49
Angiodysplasia97,98
Angiography98
Angiotensin-receptor blockers
34
Aniongapacidosis125
AnticholinergicCrises109
AnticholinergicPoisoning106
AntidepressantOverdose109
AntiretroviralTherapy85
Antizol110
Aredia140
Arfonad44
ArterialLine21
Aspirin27,28,119
Assistcontrol50
Asthma58
Atacand34
Atenolol29-31
Ativan51,123
Atracurium52
Atrialfibrillation36
Augmentin65,81
Avapro34
Azithromycin65,81,86
Azmacort59,64
AZT85
Bactrim65,84
Barbituratecoma121
Basaljel141
Beclomethasone59,64
Beclovent59,64
Betapace41,45
Biaxin65,81,86
Bisoprolol35
Blood Component Therapy
18
Bodywaterdeficit142
Bretylium115
Brevibloc39,44,115
Budesonide59,64
Bumetanide34
Bumex34
Calan38
Calcimar140
Calcitonin140
Calcium19
CalciumChloride132
Candesartan34
Capoten30,34
Captopril30,34
Cardene44
CardiacTamponade69
Cardiac-specific troponin T
26
Cardioversion41
Cardizem38
Carvedilol35
Cefizox46,82,90
Cefotan90,91
Cefotaxime82,90,92
Cefotetan90,91
Cefoxitin90
Ceftazidime82,90
Ceftizoxime46,82,90
Ceftriaxone82
Cefuroxime82
CentralIntravenousLines20
CentralVenousCatheter21
Centralvenouscatheters20
Cerebyx123
ChestTubeInsertion68
ChestTubes21
Chloride19
CholinergicPoisoning106
Chronic obstructive pulmo-
narydisease62
Cimetidine94
Cipro81,82,91,92
Ciprofloxacin81,82,91,92
Cisatracurium52
CK-MB26
CKMB26
CKMBiso26
Claforan90,92
Clarithromycin81,86
Clarithromycin 65
Clopidogrel119
Clopidogrel 27
Clotrimazole85
CocaineOverdose108
Coccidioidomycosis86
Coccidiomycosis86
ColonPolyps98
Colonoscopy97
CoLyte97
Combivir85
Congestiveheartfailure32
Cordarone41,45
Coreg35
Corlopam44
Corvert41
Coumadin57
Coumadinoverdose115
Cozaar34
Creatinephosphokinase25
Criticalcarehistory15
Criticalcarephysicalexami-
nation15
Crixivan85
Cromolyn60,61
Cryoprecipitate19,73
Cryptococcus neoformans
86
CTnl26
CTnT26
CyclicAntidepressantOver-
dose109
Cyclic Total Parenteral Nu-
trition19
Cytomegalovirus85
Cytovene85,86
Dalteparin30
Dapsone84
Decadron121
Deferoxamine111
Delavirdine85
Demadex34
Dexamethasone121
Dextrose 19
DiabeticKetoacidosis125
Didanosine85
Diflucan85,86
Digibind110
Digoxin35,39,110
DigoxinimmuneFab110
DigoxinOverdose109
Dilantin45
Diltiazem38
Diovan34
Diphenoxylate/atropine20
Diprivan49,51,123
Dipyridamole119
DischargeNote18
Disopyramide40
Disseminated intravascular
coagulation72
Diverticulardisease98
Dobutamine36,89
Dobutrex36
Dofetilide40,41
Dopamine36,88,89
Doxycycline65,81
DrugOverdose105
EACA74
Ecotrin119
Efavirenz85
Electrocardiogram25
Electrolytes18
Elevated Intracranial Pres-
sure120
Enalapril34
Enalaprilat44
EndotrachealTube49
EndotrachealTubes20
Enoxaparin30
EnteralBolusFeeding20
EnteralNutrition20
Epinephrine89
Epivir85
Erythromycin81
Esmolol39,44,115
Esophagitis85
Ethambutol86
Ethambutol 86
Ethylene Glycol Ingestion
110
Etomidate49
External jugular vei n
catheterization22
Extrapyramidal syndromes
106
Famotidine94
Famotidine 20
FatEmulsion19
Febrile Transfusion Reaction
71
Feedingtubes21
Fenoldopam44
Fentanyl49
Fibrinolytics27
Flagyl90
Flecainide40,45
Flovent59
FloventRotadisk59
Floxin81,82
Fluconazole85,86
Fluids18
Flumazenil102
Flunisolide59,64
Fluticasone59
Fomepizole110
Fortaz82,90
Foscarnet85
Fosinopril34
Fosphenytoin123
Fragmin30
FreshFrozenPlasma18
Fungizone86
Furosemide34,36,129,132,
136
Gamma Hydroxybutyrate
(GHB)111
Ganciclovir85,86
GastricLavage 105
Gastrointestinal Bleeding 93,
96
Gentamicin46,82,90,92
Glomerulonephritis128
Glycoprotein IIb/IIIa inhibitors
31
GoLytely97
Heartfailure32
Hematochezia96
Hematuria129
Hemodialysis106
Hemolytic Transfusion Reac-
tion71
Hemoperfusion106
Hemorrhoid98
Heparin28,30,56
HepaticEncephalopathy102
Herpessimplex85
Herpes Simplex Encephalitis
85
Herpesvaricellazoster85
High-dosepenicillinG82
Histoplasmosis86
History15
Hivid85
Hydralazine34,44
Hydrochlorothiazide34
Hyperaldosteronism43
Hypercalcemia139
HypercalcemicCrisis139
Hyperkalemia130
Hypermagnesemia135
Hypernatremia138
Hyperphosphatemia141
HypertensiveEmergencies41
HypertensiveEmergency41
HypertensiveUrgency42
Hyperventilation121
Hypokalemia133
Hypomagnesemia134
Hyponatremia136,137
Hypophosphatemia140,141
Ibuprofen46
Ibutilide40,41
Imdur31
Imipenem/cilastatin90-92
Imodium20
Inderal39
Indinavir85
Indocin46
Indomethacin46
INH86
Insulin126,127
Intal60,61
Integrilin31
IntermittentMandatoryVenti-
lation53
I nt er nal jugul ar vei n
cannulation22
Interstitialnephritis128
Intralipid 19
Intropin36
Intubation49
InverseRatioVentilation52
Invirase85
Irbesartan34
IronOverdose111
IschemicColitis98
IschemicStroke117
Isoniazid86
Isopropyl Alcohol Ingestion
112
Isoproterenol45
Isoptin38
Isordil31,34
Isosorbide34
Isosorbidedinitrate31
Isosorbidemononitrate31
Isuprel45
Itraconazole86
Jevity20
Kaopectate20
Kayexalate130,132
Kefurox82
Ketoconazole85
Ketorolac46
Kussmaul'ssign69
Labetalol43
Lactulose103
Lamivudine85
Lanoxin39
Lasix34,36,132
Levalbuterol59
Levaquin65,81,82,92
Levofloxacin65,81,82,92
Lidocaine45
Linezolid90
Linton-Nachlastube95
Lisinopril29,34
LithiumOverdose112
Lomotil20
Loperamide20
Lopressor29-31,35,39
Lorazepam51,123
Losartan34
Lovenox30
Low-molecular-weight hepa-
rin57
Lower Gastroi ntesti nal
Bleeding96
Lung volume reduction sur-
gery65
Magnesium19,126,135
Magnesiumoxide135
Magnesiumsulfate44
Mallory-WeissSyndrome94
Mannitol121
Maxair63
Maxipime91
Mefoxin90
Melena96
Meningitis75
Meropenem82,90
Merrem82,90
Metabolicacidosis125
MethanolIngestion113
Methylprednisolone61
Metoclopramide20
Metolazone34
Metoprolol29-31,35,39
Metronidazole90
Mexiletine45
Mexitil45
Mezlocillin90
Miacalcin140
Midazolam49-51,123
Milrinone36
Monopril34
Montelukast59,60
Morphine26,51
Morphinesulfate26,36
Motrin46
Mucomyst107
Multi-Trace Element For-
mula19
Multiple organ dysfunction
syndrome87
Mycelex85
MycobacteriumAviumCom-
plex86
Mycobutin86
Myocardialinfarction25
Myoglobin26
N-Acetyl-Cysteine107
Nafcillin46
NarcoticPoisoning106
NasogastricTubes21
NasotrachealIntubation50
Natrecor36
Natriureticpeptides36
Nedocromil60,61
Nelfinavir85
Neo-Synephrine)50
Neomycin103
Nesiritide36
Neutral phosphate (Nutra-
Phos)141
Nevirapine85
NewYorkHeartAssociation
Criteria33
Nicardipine44
Nimbex52
Nipride43
Nitrates29
Nitroglycerin26,43
Nitroglycerinpatch31
Nitroglycerinsublingual31
Nitroglycerine29,36
Nitroglycerineaerosol31
Nitroprusside43
Nizoral85
Non-aniongapacidosis125
NonQ-waveMI25
NonQ-wave myocardial
infarction30
Norcuron51
Norepinephrine89,115
Normodyne43
Norvir85
NTG31
Nutra-Phos141
Octreotide95,102
Ofloxacin81,82
Oliguria127
OralCandidiasis85
OrotrachealIntubation49
Osmolality,estimateof142
Osmolite20
Oxacillin46
Pacemakers46,47
PackedRedBloodCells18
Pamidronatedisodium140
Pancreatitis99
Pancuronium52
Paracentesis91
ParenteralNutrition19
Pavulon52
Pentamidine84
Pepcid20,94
Percutaneous coronary inter-
vention29
Pericardiocentesis46,69
Pericarditis45
Per i pher al Par ent er al
Supplementation19
Peritonitis91
Phenobarbital123
Phentolamine44
Phenylephrine89,115
Phenytoin45,123
Phosphate19,126,141
PhysicalExamination15
Piperacillin90
Piperacillin/tazobactam 82,
90-92
Pirbuterol63
Pitressin95
Platelets18
Plavix27,119
PleuralEffusion65
Pneumocystiscariniipneumo-
nia83
Pneumonia79
Pneumothorax67
Poisoning105
Polyethyleneglycol-electrolyte
solution97
Posturalhypotension93
Potassium19,126
PRBC18
Prednisolone61
Prednisone46,61,84
Pressure Support Ventilation
53
Primacor36
Primaxin90-92
Prinivil29,30,34
Procainamide39,40,44
ProCalamine19
ProcedureNote17
ProgressNote17
Promix20
Propafenone40,41,45
Propofol49,51,123
Propranolol39
Proteinpowde20
Proventil59,63
Pseudohyperkalemia131
Pseudohyponatremia136
Pulmicort59,64
Pulmocare20
Pulmonaryarterycatheter20
P u l m o n a r y A r t e r y
Catheterization23
Pulmonaryarterypressure24
Pulmonaryembolism54
PurulentPericarditis46
Pyrazinamide86
Pyridoxine86,110
Pyrimethamine86
Q-wave myocardial infarction
25
Quinapril34
Quinidine39,40
Quinupristin/dalfopristin90
Radiofrequencycatheterabla-
tion41
RadiographicEvaluation20
Radionuclidescanorbleeding
scan97
Ramipril34
Ranitidine20,94
Ranson'scriteria101
Reglan20
Renalfailure127
ReoPro31
Reperfusiontherapy27
Rescriptor85
RespiratoryFailure50
Reteplase30
Retitine44
Retrovir85
Rifabutin86
Rightatrialpressure24
Ringer'slactate69
Ritonavir85
Romazicon102
Rythmol45
SalicylateOverdose113
Salmeterol59,63,64
Sandostatin95
Saquinavir85
SecondaryHypertension42
Sepsis87,89
Septicshock87
Septra65,84
Serevent59,63,64
Sildenafil29
Singulair59,60
Slo-Bid60
Slo-Mag135
Sodium19,126,136
SodiumBicarbonate132
So di um pol y s t y r e n e
sulfonate130,132
Solu-Medrol61
Sotalol40,41,45
Spironolactone34
Sporanox86
Spot urine sodium concen-
tration129
ST-segmentdepression25
ST-segmentelevationinfarc-
tion25
Starvationketosis125
StatusEpilepticus122
Stavudine85
Streptase29
Streptokinase29
Stroke117
Subclavian vein cannulation
23
Sublimaze49
Succinylcholine49
Sulfadiazine86
Sulfonamide81
Sustiva85
Sympathomimetic Poisoning
106
Synercid90
Systemic inflammatory re-
sponsesyndrome87
t-PA29,117
Tagamet94
Tambocor45
Tamponade69,95
Tenectaplase30
Tenormin29-31
TensionPneumothorax68
Tetracycline81
Theo-Dur60
Theophylline60,61,64
TheophyllineToxicity114
Thiamine123
Thrombol yti c-associ at ed
Bleeding73
Thrombolytics28
Ticarcillin90
Ticarcillin/clavulanate 82,
90-92
Tikosyn41
Tilade60,61
Timentin82,90-92
Tirofiban31
Tissueplasminogenactivator
29,57,117
Tobramycin46,90,92
Tocainide45
Tonocard45
Toradol46
Torsadesdepointes44
Torsemide34
ToxicSeizures106
Toxicologic Syndromes106
Toxicology105
Toxoplasmosis86
tPA30,57
Tracheostomies21
Tracrium52
Transfusionreaction71
Transjugular Intrahepatic
PortacavalShunt 95
Trauma67
Triamcinolone59,64
Tricyclic antidepressant
overdose109
Trimethaphan44
Trimethoprim/SMX65,84
Tr i me t h o p r i m/ s u l f a -
methoxazole81
Troponin26,33
Tuberculosis86
inaids86
TypeandCrossMatch18
TypeandScreen18
Unasyn82,90,91
Unfractionatedheparin56
Unidur60
Unstableangina25,30
Upper Gastroi ntesti nal
Bleeding93
Urinalysis129
Valacyclovir85
Valsartan34
Valtrex 85
Vanceril59
Vancocin82
Vancomycin46,82,90
Vanc omyci n- r esi s t ant
enterococcus90
Variceal95
Varicealbleeding94
Varicealhemorrhage95
Varicella85
Vasopressin95
Vasotec34,44
Vecuronium51
Ventilation-perfusion Scan
55
Ventilator Management 50,
51
VentilatorWeaning52
Ventolin59,63
Ventriculararrhythmias44
Ventricularfibrillation44
Ventriculartachycardia44
Verapamil38
Versed49-51,123
Viagra29
Vibramycin65
Videx85
Viramune85
VitaminB1219
VitaminK19,115
Warfarin57
Warfarinoverdose115
Waterexcess139
WeaningProtocols53
WholeBowelIrrigation105
WithdrawalSyndrome106
Wymox65
Xopenex59
Zafirlukast60
Zalcitabine85
Zantac20,94
Zaroxolyn34
Zebeta35
Zerit85
Zestril34
Ziagen85
Zidovudine85
Zileuton60,61
Zinacef82
Zithromax65,81,86
Zoster85
Zosyn82,90-92
Zovirax85
Zyflo60,61
Zyvox90