Critical Care
Thromboembolic Events During Continuous Vasopressin
Infusions: A Retrospective Evaluation
Bruce A Doepker, Maria R Lucarelli, Amy Lehman, Mary Beth Shirk
Arginine vasopressin is an endoge-
nouspeptide hormonereleased from
t~e hypothalamus and stored in the poste-
nor pituitary gland. It stimulates both va-
sOpressin 1. (VI.) and vasopressin 2 (V1)
receptors located in vascular smooth mus-
cleandrenal tissues.' Activation of VI. re-
ceptors can causedirect and indirect vaso-
COnstriction in the skin,softtissue, skeletal
muscle, fat tissue, pancreas,and thyroid
gland.1 VI. receptor activation can alsoin-
dUce an increase in intracellular calcium,
~ereby facilitating thrombocyte aggrega-
tion. Vasopressin may increase factor VITI
COagulant and von Willebrand factor by
activating the V1 receptor.'? Desmo-
pressin, a synthetic analog of vasopressin,
hasbeenassociated withboth arterial and
Venous thrombosis. Desmopressin and va-
soPressin possess someof thesamecoagu-
lant properties. Rapidrelease of coagulants
from the vascularendothelium can cause
platelet aggregation and increase shear
fOre es in . arteries, leading to thrombosi .
SIS in between the2 arms (p = 0.72).
both cardiac andcerebral vesselsr"
A synthetic form of naturally occurring
vasopressin has been used clinically to
treatdiabetes insipidus and variceal hem-
orrhage.l1 Interest in its use for hemo-
dYnamic support in patients with septic,
hemorrhagic, and cardiogenic shock is
~OWing,'2'16 Hypovolemia and hypoten-
SIOn experienced during shock trigger the release of en-
dogenous vasopressin. Late in septic shock, one-third of
--~-------------------
Author information provided at the endof the text.
wwwtheannalscom
BACKGROUND: Published guidelines suggest thatvasopressin has a rolein shock
treatment, although its safety has not been adequately evaluated in a clinical
setting. Vasopressin causesplatelet aggregation and has been associated with
the release of factor VIII coaqulant and von Willebrand factor.
OBJECTIVE: To compare the incidence of venous thromboembolism (VTE) in
patients with a diagnosis of shockwho received vasopressin with thosewho did
not receive vasopressin for hemodynamic support.
METHODS: A retrospective, single-center, cohort study was conducted at an
academic, tertiary carecenter with350 patients with a diagnosis of shock. Patients
from theintensive care unitwererandomly selected andseparated into2 groups for
comparison of those receiving only catecholamines with those receiving
vasopressin with or without catecholamines for hypotension. Patients withdiabetes
insipidus or variceal hemorrhage andthosewith any documented history of VTE
wereexcluded. The primary outcome, VTEoccurrence, was defined as a positive
Doppler ultrasound, spiral computed tomography, or documented diagnosis in the
discharge records. Frequency and type of risk factors for VTE were compared
between the 2 studyarms. A riskfactor modeling approach was performed, using
logistic regression to identify potential confounders and effect modifiers in the
relationship between vasopressin andVTE.
RESULTS: There were 175patients in each armof the study. Thecrude incidence of
VTE was7.4%and8% in the vasopressin andcatecholamine groups, respectively
(p =0.84). No significant difference in the incidence of deep venous thrombosis
(vasopressin 5.1 %, control 7.4%; p = 0.51) or pulmonary embolism (vasopressin
2.3%, control 0.6%; p = 0.37) was found between groups. After adjusting for
covariates, therewas no statistically significant difference in the incidence of VTE
CONCLUSIONS: This investigation provides initial evidence that vasopressin
infusions do not increase the riskof VTEin patients with shock.
KEY WORDS: critical care, hemodynamics, hypotension, sepsis, vasopressin,
venous thromboembolism.
Ann Pharmacother 2007;41 :1383-9.
Published Online, 7 Aug 2007, www.theannals.com. DOI10.1345/aph.1H498
patients have inappropriately low vasopressin levels. Al-
though several theories attempt to explain this depletion,
the relative deficiency can best be describedas a decrease
in synthesis due to a bluntedresponse to systemic hypoten-
sion and osmotic changes,":"
TheAnnals ofPharmacotherapy • 2007September, Volume 41 • 1383
BA Doepker et al.
Vasopressin's placein the treatment of shockis as yet un-
defined,in part due to unknownassociated adverseeffects.
One concern is its effect on coagulation. Jn a retrospective,
cohort, single-center study, Hall et aJ.2° compared a fixed
dose of vasopressin (0.04units/min; n =50) with dopamine
(n = 51) and norepinephrine (n = 49) as initial vasopressors
in septic shock. No difference was found in mean arterial
bloodpressure, the primary outcome, 1 hourafterthe startof
the vasopressor infusion.The incidence of venous throm-
boembolism (VTE),a secondary outcome,was found to be
higher in patients who received vasopressin (14%) than in
thosewho received norepinephrine (2%)or dopamine (8%).
This study was not adequately powered to evaluatethe co-
agulopathic effects of vasopressin.
Our study comparedthe incidence of VTE in patients in
the intensive care unit (JCU) with a diagnosis of shock
who received vasopressin with those who did not receive
vasopressin for blood pressure control.
Methods
A retrospective, single-center, cohort study was con-
ducted. Patients 18 years of age or older were included if
they were admitted to the surgical or medical JCUs be-
tween September 2001 and June 2004. All patients with
the International Classification of Disease-9(ICD-9) code
for shock were eligible for review. Exclusioncriteria were
the use of vasopressinfor any indicationother than shock
(eg, diabetes insipidus, variceal hemorrhage), any docu-
mented history of VTE prior to vasopressin or cate-
cholaminetherapy, activetreatment for VTE, and pregnan-
cy.Those identified for study were separated into 2 groups:
patients who received a vasopressin infusion with or with-
out a catecholamine and those who received only a cate-
cholamine (eg, epinephrine, norepinephrine, phenyle-
phrine, dopamine) or a combination of catecholamines
without vasopressin. The patients in each arm were then
numbered sequentially and selected for screening against
inclusionand exclusion criteria using a computer-generat-
ed random number table by simple randomization. The in-
stitutional review board at The Ohio State University ap-
provedthe study by expeditedreview.
The following baseline demographic information was
compared between groups: age, sex, type of JCU, Acute
Physiology and Chronic Health Evaluation (APACHE) II
scoreon lCU admission, lCU admission diagnosis, form of
VTE prevention on initiation of vasopressor therapy, and
type of shock determined by ICD -9 codes and medical
recordreview. VTE prevention was categorized as full sys-
temic anticoagulation, prophylacticanticoagulation, or no
documented methodof prevention. The type and frequency
of risk factors for VTE werecompared between groups"
Respiratory failure was defined as abnormal respiratory
function diagnosed by lab tests or physicianclinicaljudg-
1384 • The Annals of Pharmacotherapy • 2007September, Volume 4J
ment for the need of mechanical ventilation. Obesity was
defined as a body mass index greater than or equal to 30
for males and 28.6 for females. History of VTE was con-
sideredto be any previous diagnosis of deep vein thrombo-
sis (DVT) or pulmonary embolism (PE) as noted in the
medical record or by ICD -9 code. VTE screeningwas not
routinely performed during the study period. Diabetes in-
sipidus and variceal hemorrhage were identified by medi-
cal record or ICD -9 code review during the patient's hos-
pital stay. Doses for individual catecholamines were com-
pared between groups as total dose in milligrams
administered per admission body weight (kg). ICU and
hospital length of stay and mortality were compared be-
tween study arms.
The primaryendpoint was identification of VTE during
vasopressin or catecholamine therapy. VTE was defined as
a positive Dopplerultrasound, spiral computedtomography
(CT),or a documented diagnosis in the discharge summary.
Secondary endpoints were acutemyocardial infarction (MI)
or embolic stroke during vasopressin or catecholamine in-
fusion and the incidence of VTE in patients who received
infusions at ratesgreaterthan0.04 units/min for longerthan
1 hour compared with thosewho received lessthan or equal
to 0.04 units/min. VTE incidence was also compared be-
tween patients who received greater than 0.1 units/min and
those receiving less than or equal to 0.1 units/min for at
least 1 hour. MI was considered to be present if a patient
had an elevated troponin and documentation of MI in the
medical record. Embolicstroke was identified by reviewof
CT scans,MRI reports, and medical records.
STATISTICAL ANALYSIS
The sample size for this study was calculated to achieve
at least 80% power in detecting a 9% difference in the inci-
dence ofVTE between the 2 arms, using an a = 0.05 level
of significance. Estimated group proportions used in the
samplesize calculations were basedon the studyby Hall et
al.20 At least 166 patients were needed in each group to
achieve the desired power. Baseline characteristics were
first compared between the 2 groups. Categorical data
were analyzedusing X2 tests or Fisher's Exact test. Contin-
uous variables were analyzed using a 2 sample t-test or
Mann-Whitney U test for nonparametric data if 'the as-
sumption of normality was violated. Statistical signifi-
cance was defined as a p value less than or equal to 0.05.
Logistic regression models were applied to the data for
both treatment arms to control for differences in covariates
that may have confounded the relationshipbetween vaso-
pressin and VTE. With the use of a risk factor modeling
approach, variables were entered for control only if they
changed the crude odds ratio (OR) for VTE by at least
15-20%.22 After all confounders were identified,the pres-
ence of significanteffect modifierswas determined by as-
www.theannals.com
 sessing the statistical significance of the 2 way
Table 1. Patient Characteristics
interaction with vasopressin. From the model,
Vasopressin Arm Control Arm
the adjustedOR and 95% confidence interval Characteristic =
(n 175) =
(n 175) pValue
(CI) for VTE were calculated for the vaso- Age, y
pressin and catecholamine groups. All statisti- mean±SD 58.6 ± 15 60 ± 16 0.41
cal analysis was performed using SAS soft- range 19 to >89 19 to >89
Ware, version 9.1 (SAS Institute, Cary, NC). Male, n (%) 110 (62.9) 105 (60) 0.66
Weight, kg
mean ±SD 86.3 ±26.1 82.2 ±25.9 0.15
ReSUlts range 46-195 37-213
ICU pts., n (% )
A total of 473 patients were evaluated for medical 119(68) 137 (78.3) 0.04
inclusion in the study. However, 123 were ex- surgical 56 (32) 38 (21.7) 0.04
Diagnosis, n (%)
clUded (vasopressin arm: 40 prior VTE, 11 al-
cardiovascular 52 (29.7) 32 (18.3) 0.02
ternative indications, 6 other; control arm: 51 respiratory 39 (22.3) 43 (24.6) 0.71
prior VTE, 1 pregnant, 14 other). Each arm infectious 33 (18.9) 43 (24.6) 0.24
wascomprised of 175 patients. Patientcharac- malignancy 19 (10.9) 18 (10.3) 0.86
GI hemorrhage 7 (4) 6 (3.4) 0.78
teristics were similarbetweenthe 2 arms, with
hepatic insufficiency 10 (5.7) 6 (3.4) 0.44
differences shown in Table 1. Data on length renal insufficiency 3 (1.7) 8 (4.6) 0.22
of stay and mortality are included in Table 2. other 11 (6.3) 19 (10.9) 0.18
The total amount of each catecholamine per APACHE II score"
admission body weight was compared as a mean ± SD (range) 34 ±8 (3-62) 30 ±9 (6-52) 0.0001
Shock type, n (%)
meanvaluebetweenthe 2 arms; no significant septic 108 (61.7) 123 (70.3) 0.11
difference was shown. Fifty-three (30.3%) pa- cardiogenic 54 (30.9) 39 (22.3) 0.09
tients who received vasopressin were given hypovolemic 9 (5.1) 6 (3.4) 0.6
doses that exceeded0.04 units/min for at least distributive 4 (2.3) 7 (4) 0.54
Type of anticoagulation or
1 hour and 33 (18.9%) received doses greater DVT prophylaxis, n (%)
than 0.1 units/min for at least I hour. systemic 33 (18.9) 41 (23.4) 0.36
InCidence of VTE (DVT and PE) was simi- prophylactic 86 (49.1) 89 (50.9) 0.83
=
lar in the vasopressin arm (n 13, 7.4%) and none documented 56 (32) 45 (25.7) 0.24

the Control arm (n = 14,8%; p =0.84). Diag- VTE risk factors, n (%)21
immobility 173 (98.9) 174 (99.4) 1.0
nosticstudies confirmed VTE in 23 of 27 pa- central venous catheter 164 (93.7) 153 (87.4) 0.07
tients, with4 of 27 identified in patients' medi- age >40 y 157 (89.7) 152 (86.9) 0.51
ca!records. VTE was further analyzed to com- respiratory failure 125 (71.4) 126 (72) 0.91
surgery 56 (32) 24 (13.7) 0.0001
Pare the incidence of DVT and PE individually.
obesity 55 (31.4) 46 (26.3) 0.35
Nine (5.1 %) vasopressin patients and 13(7.4%) CHF 44 (25.1) 47 (26.9) 0.81
Control patients developed a DVT (p = 0.51). malignancy 44 (25.1) 44 (25.1) 1.0
Therewas no significant difference in the inci- cancer treatment 16 (9.1) 11 (6.3) 0.42
13 (7.4) 9 (5.1) 0.51
dence of PE (vasopressin: n = 4, 2.3%;control: smoking
other 4 (2.3) 6 (3.4) 0.75
n =: 1,0.6%; p = 0.37). In a subgroupanalysis
to determine whetherVTE was more common APACHE II = Acute Physiology and Chronic Health Evaluation; CHF = congestive
heart failure; DVT = deep vein thrombosis; GI = gastrointestinal; ICU = intensive
in surgery patients, it was found that 9 of 80 care unit; VTE = venous thromboembolism
01.3%) surgical patients and 18 of 270 (6.7%) BHigherscores reflect more severe critical illness; scores can range from 0-71.

nonsurgery patients developed a VTE (p =

0.27). The method of anticoagulation used for
patients Who developed a VTE was analyzed. Table 2. Length of Stayand Mortality
In patients who developed VTE, 25.9% re-
Vasopressin Arm Control Arm
ceiVed full systemic anticoagulation, 40.7%re- Parameter (n = 175) (n = 175) pValue
ceived Prophylaxis, and 33.3% had no docu- Hospital length of stay, days
mented Prophylaxis. Patientsdeveloped an MI median (range) 16 (0.5-188) 15 (0.5-112) 0.32
= =
1.7% (n 3) and 2.3%(n 4) of the timein the ICU length of stay, days

vasopressin and controlarms, respectively (p =

median (range) 9 (0.5-66) 10 (0.5-83) 0.96
mortality, n (%) 136 (77.7) 83 (47.4) 0.0001
0.7), One (0.6%) patient in the vasopressin arm
ICU = intensive care unit.
and no patients(0%) in the control arm devel-

wwwtheannalscom TheAnnalsofPharmacotherapy • 2007September, Volume 41 • 1385

BA Doepker et 01.
oped an embolic stroke (p = 0.32) (Figure 1). Of the 14 pa-
tients who received vasopressin and developed a VTE, 5
(35.7%) received vasopressin at an infusion rate greater
than 0.04 units/min for at least 1 hour. When all of the pa-
tients who received vasopressin at a dose greaterthan 0.04
units/min (n =53) werecompared withthe patients who re-
ceived vasopressin at doses less than or equal to 0.04
units/min (n = 122), therewas stillno significant difference
in the incidence of VTE (9.4% vs 6.6%, respectively; p =
0.72). The incidence of VTEin patients who received doses
greater than 0.1 units/min was 9.1% (3/33), compared with
7.0% (10/142) in p';rtients who receiveddoses less than or
equal to 0.1 units/min (p =0.97).
Although the incidence of VTE between the vasopressin
and control groups was not significantly different, there
weredifferences betweenthe 2 groups in the incidence of
certain risk factors (surgery, APACHE II score,cardiac dis-
ease) that may have affected the comparison. Therefore, a
risk factor modeling approach was performed to identify
potentialconfounders and effect modifiers between vaso-
pressin and VTE. After adjusting for APACHE II score,
cardiac disease, and surgery, there was still no significant
difference in the incidence of VTE between the 2 arms
(OR =1.157,95% CI 0.528 to 2.534; p =0.72). No other
confounders or effectmodifiers were identified.
Discussion
Small studies in several patient populations diagnosed
with shock have supported vasopressin's efficacy,but its
safetyneeds to be further established.P'" Desmopressin is
structurally related to vasopressin and is used for sponta-
neousor trauma-related bleeding in patients with a diagno-
sis of hemophilia A or type 1 von Willebrand disease."
Logically, when evaluatingthe safety of vasopressin, one
9 8
8 7.4
7 o Control
6
~
5
0
4
3
2
1
0
VTE DVT
Figure 1. Incidence of VTE,DVT, PE, MI, and embolicstrokein the vasopressin and controlarms.No significant differences were foundbetween the
2 armsforVTE (p = 0.84), DVT (p =0.51), PE (p = 0.37), MI (p = 0.7), or embolicstroke (p = 0.32).
VTE = venousthromboembolism; DVT = deep veinthrombosis; PE = pulmonary embolism; MI = myocardial Infarction
1386 • The Annals of Pharmacotherapy • 2007September, Volume 41
mustconsider its effects on coagulation. Early studies with
vasopressin found an increase in factor vm coagulant and
von Willebrand factor,"? In addition to the retrospective
study by Hall et al.,20 the effectsof vasopressin on the co-
agulation systemin patients with vasodilatory shock were
prospectively evaluatedby Dunseret a1.3 This study com-
pared patients who receivedan arginine vasopressin infu-
sion (n =21) with thosewho received a norepinephrine in-
fusion alone (n =21). Platelets, factor VIII coagulant, von
Willebrand, and ristocetin cofactors were measured at
baseline, I hour, 24 hours, and 48 hours after randomiza-
tion. Platelet count differed between the 2 groups (p =
0.036) and the authors concluded that vasopressin intra-
venous infusion may cause platelet aggregation and induce
thrombocytopenia in patients with vasodilatory shock.
NeitherHall et a1.20 nor Dunseret al,' adequately powered
theirstudies to evaluate the development of VTE.
Vasopressin's coagulopathic effects arebelieved to be due
to its activity on the V2receptors and are more commonly
reported with infusion rates greaterthan 0.1 units/min, but
also have been observed when doses exceed 0.04
units/min. 1I ,28,29 We were not able to identifya statistically
significantdifference in the developmentof VTE using a
breakpointof either 0.04 or 0.1 units/min. No other study
has specifically addressed the development of VTE over a
range of doses.
Limitations
Our studyrepresents the first adequately powered study
to evaluate the coagulopathic safety of vasopressin in the
treatment of shock.Although we ensuredadequate sample
size, our investigation does have limitations. This was a
retrospective, single-center study. Althoughwe were able
to select patientsrandomly from an identified population,
• Vasopressin
PE MI Stroke
wwwsheannalscom

we were not able to randomly assign subjects to the treat-
mentgroupsin a prospective, balancedmanner.
An increased number of patients receiving vasopressin
had the VTE risk factor of surgery; however, the incidence
of VTE was not greater in this arm. The vasopressin group
alsoincludedmore patientsadmitted with a cardiovascular
diagnosis, highermean APACHE II score,and highermor-
talityrate. Because of the relationship between APACHE
IT scoresand mortality, one would expect to see an imbal-
ance of both. One explanation for these differences is the
wayin which vasopressin is used at our institution. It is not
Considered a first-line agent, but rather a salvage therapy,
andis initiated later in the courseof shockafter other vaso-
pressors have failed. Using a retrospective design, one
~_ould therefore expect higher APACHE II scores (and
SUbsequently higher mortality) in the vasopressin treatment
group. To control for the above-stated variables, which
may have influenced the relationship between vasopressin
and VTE, logisticregression was applied.Using a logistic
regression model, we controlled for the differences be-
tween the 2 arms and still found no significant difference
in the incidence of VTE betweenpatients who receivedva-
sopressin and those who did not.
Cook et al.30 reported that the highest incidenceof low-
er-limb DVT occurs within the first 5 days of admission to
a medical-surgical ICU. We identified 3 patients with
ym (23%) in the vasopressin arm and 3 (21%) with VTE
In the catecholamine arm in the first 5 ICU days. In addi-
tion, there was no statistically significant difference in 5
dayICU mortality betweenthe 2 treatment groups.
It is not known whetherthe incidence of VTE is a dose-
related phenomenon. Because we were not able to
~rospectively control the vasopressin dose, we retrospec-
t~vely categorizedand analyzed doses administeredto pa-
tients.Thirty percent of our study patients received vaso-
pressin infusions greaterthan 0.04 units/min and 18.9%re-
ceived doses greater than 0.1 units/min. Therefore, we
reported the incidenceof VTE for all doses and then sepa-
rately analyzed doses greater than 0.04 and 0.1 units/min
andfoundno differences.
The retrospective design of this investigation did not
perrnitus to control for the presence or type of VTE pre-
vention or treatment that patients received. We found no
dOCumentation of any type of VTE prevention for a greater
nUmber of patients than expected, and we were unable to
COnfllln whether this reflected an oversight in prescribing
or simplyincomplete documentation. However,the lack of
dOCumentation for VTE preventionwas balancedbetween
groups. In addition, we chose to include patients who re-
C~ived fuII systemicanticoagulation. This permittedanaly-
SIS of a real-world sample of patients who received vaso-
pressin. Patientswith and without full systemicanticoagu-
I arIon were balanced between the arms. Finally, the
WWw.theannals.com TheAnnals ofPharmacotherapy • 2007September, Volume 41 • 1387
Thromboembolic EventsDuringContinuous Vasopressin Infusions
distribution of types of prophylaxis was similar in patients
who developedVTE and in those who did not.
Conclusions
Previous studies have demonstrated that vasopressin
causes coagulopathic changes.However, no previous stud-
ies have been conducted to measure this in the setting of
shock; therefore,its use is recommended only for patients
not responding to catecholamines. In this retrospective
study, vasopressin administered as a continuous infusion,
with or withoutcatecholamines, for hemodynamic support
of shockdid not increasethe incidenceof VTE when com-
pared with catecholamines administered without vaso-
pressin. Prospective studies are warrantedto further evalu-
ate the risks of using vasopressin for the treatment of
shock.
Bruce A Doepker PharmD, Specialty Practice Pharmacist, Criti-
cal Care, Department of Pharmacy, The Ohio State University Med-
ical Center, Columbus, OH
~arla R Lucarelli MD, Assitant Professor-Cllnical, Pulmonary/Crit-
IcalCare, Internal Medicine, TheOhioState University Medical Center
Amy Lehman MAS, SeniorConsultinq Research Statistician, Cen-
ter for Biostatistics, The Ohio State University
Mary Beth Shirk PharmD, Specialty Practice Pharmacist, Emer-
gency Medicine, Department of Pharmacy, The Ohio State Univer-
sity MedicalCenter
Reprints: Dr. Doepker, Department of Pharmacy, The Ohio State
University Medical Center, Room368, DoanHall, 410 W. 10thAve.,
Columbus, OH 43210, fax 614/293-3165, bruce.doepker@os-
umc.edu
WethankAnthonyGerlachPharmD, LindsayPell PharmD, and JamesVisconti PhD
for their critical review of this article.
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25. DunserMW,Mayr AJ, UlmerH, et al. Arginine vasopressin in advanced
vasodilatory shock: a prospective, randomized, controlled study. Circula-
tion2003;107:2313-9.
26. Dunser MW, MayrAJ, Tur A,et aI.Ischemic skinlesions asa complication
of continuous vasopressin infusion in catecholamine-resistant vasodilatory
shock: incidence andriskfactors. CritCareMed2003;31:1394-8.
27. Lethagen S. Desmopressin(DDAVP) and hemostasis. Ann Hematol
1994;69:173-80.
28. Obritsch MD,Jung R, Fish DN, MacLaren R. Effects of continuous va-
sopressin infusion in patients with septic shock. Ann Pharmacother
2004;38:1117-22. Epub3 Jun 2004.DOl 1O.l345/aph.1D513
29. HollenbergSM, Ahrens TS, Annane D, et aI. Practice parametersfor
hemodynamic support of sepsisin adultpatients: 2004update. CritCare
Med2004;32:1928-48.
30. CookD, Crowther M, MeadeM, et al. Deepvenous thrombosis in medi-
cal-surgical critically ill patients: prevalence, incidence, and riskfactors.
CritCareMed2005;33:1565-71.
Eventos Tromboemb6licos Durante Infusiones Continuas de
Vasopresina: Una Evaluaci6n Retrospectiva
BADoepker, MR Lucarelli, A Lehman, y MB Shirk
Ann Pharmacother 2007;41:1383-9.
EXTRAcro
TRANSFONDO: Gulas publicadassugieren que el uso de la vasopresina
tiene un papel en el tratamientode shock, aunque su seguridad no lia
sido evaluada adecuadamenteen situacionesclfnicas.Vasopresina causa
1388 • TheAnnals ofPharmacotherapy • 2007September, Volume 41
la agregaci6nde plaquetas y este ha side asociada con la producci6nde
los factores de coagulaci6nVlll y von Willebrand.La producci6nde
estos coagulantespuede aumentar el riesgo al desarrollo de trombosis en
vasos sangufneos.
OBJETIVO: Comparar la incidenciadel tromboembolismovenoso (TEV)
en pacientescon una diagnosis de shock que recibieron vasopresinay
que no recibieronvasopresinapara asistenciahemodinamica.
METODOS: Un estudio retrospectivo,de un solo centro, fue conducido en
un grupo de 350 pacientesque fueron seleccionadosde una manera
aleatoria de una unidad de cuidado intensivoy con una diagnosis de
shock en un centro academicode cuido terciario.Se separaron a los
pacientesen 2 grupos para comparaci6n:aquellos que recibieron
solamentecatecolaminasy aquellosque recibieron vasopresinacon 0 sin
catecolaminaspara hipotensi6n.Se excluyeron pacientesque tenfan
diabetes insipidus 0 hemorragia por varices y aquellosque tenfanuna
historia documentadade TEV.EI resultado prirnario,que era la
ocurrenciade TEV,fue definido como un resultado positivo de
ultrasonidoDoppler,tomograffacomputarizadahelicoidal,0 diagnosis
documentada en los archivos de descarga.Se compar6 la frecuencia y el
tipo de factores de riesgo para el TEV entre los dos brazos del estudio.
Se desarroll6un modelo de factor de riesgo utilizandoregresi6n
logfsticapara identificarfactores de confusi6npotencialesy
modificantesdel efecto de relaci6n entre vasopresinay TEV.
RESULTADOS: Se incluy6 175 pacientesen cada brazo de estudio. La
incidenciacruda del TEV era de un 7.4% Y 8% en los grupos de
vasopresinay catecolaminas,respectivamente(p = 0.84). No se encontr6
ningunasdiferenciasen la incidenciade trombosis venosa profunda
(vasopresina5.1%; control 7.4%; p =0.51) 0 embolia pulmonar
(vasopresina2.3%; control 0.6%; p = 0.37) entre los 2 grupos. Despues
de ajustes en las covariables,no se not6 diferenciassignificativas en la
incidenciade TEV entre los 2 brazos (p = 0.72).
CONCLUSIONES: Esta investigaci6nproporcionaevidencia inicialque las
infusionesde vasopresinano aumentan el riesgo de TEV en pacientes
con shock.
Traducido por Carlos da Camara
Evenements Thromboemboliques lors d'Infusions Continues de
Vasopressine: une Evaluation Retrospective
BA Doepker, MRLucarelli, A Lehman, et MB Shirk
AnnPharmacother 2007;41:1383-9.
REsUME
INTRODUCTION: Les recommandationsactuellessuggerentun rOle pour la
vasopressinedans Ie traitementdu choc malgre une innocuitenon
adequatementevaluee. La vasopressinefavorisel'agregation
plaquettaireet est associee IIla liberationendothelialedu facteur vm et
de VonWillebrand.
OBJECTIF: Comparer l'incidence de thromboembolieveineuse (TV) chez
les patients avec un diagnostic de chocayant recu la vasopressineIIcelle
de patients n'ayant pas recu la vasopressinepour un support
hemodynamique.
METuODOLOGIE: Une etude de cohorte retrospectivefut conduiteaupres
de 350 patients de soins intensifsselectionnesau hasard avec un
diagnostic de choc dans un seul centre academiquetertiaire.Les patients
furent separes en 2 groupes pour comparaison, soit ceux ayant recu
seulementdes catecholamines et ceux ayant recu de la vasopressineavec
ou sans catecholaminespour Ie traitementde l'hypotension. Les patients
avec diabete insipideou varices oesophagienneset ceux avec une
histoire documentee de TV furent exclus, Le resultat primaire,
l'incidence de TV,fut defini par un ultrason doppler positif, par une
tomographie spirale positive,ou un diagnosticdocumente lors du'conge
du patient. La frequence et Ie type de facteurs de risque de TV furent
compares entre les 2 groupes, Une approche des facteurs de risque par
modelisationfut effectueeen utilisantla regressionlogistiquepour
identifierles variablesconfondantespotentielIes dans la relationentre
l'utilisation de la vasopressineet la presence de TV.
wwwiheannalscom
 Thromboembolic EventsDuringContinuous Vasopressin Infusions
REsULTATS: Centsoixsante-quinze patients furentindus dans chaque CONCLUSIONS: Cette investigation nousdonneune evidence preliminaire
groupe de l'etude. L'incidence brutede TV fut de 7.4%et de 8% dans que les infusions continues de vasopressine n'augmentent pas Ie risque
les groupe, vasopressine et catecholamines, respectivement (p =0.84). de TV chezles patients en choc.
Aucune difference dans l'incidence de thrombose veineuse profonde
(vasopressine 5.1%,controle 7.4%;p =0.51)au d'emboliepulmonaire Traduitpar MarcM Perreault
(vasopressine 2.3%,contrOle 0.6%;p = 0.37) ne fut observee entreles
g;o~pes. Apresavoirajustepourles co-variables, aucunedifference
slgruficative dans l'incidencede TV ne fut observee (p =0.72).

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