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Indian J. Anaesth. 2003 SETHI, SHARMA, MOHTA, TYAGI ; 47 (5) : 345-359 : SHOCK 345 SHOCK A SHORT REVIEW Dr.

. A. K. Sethi 1 Dr. Prakash Sharma 2 Dr. Medha Mohta 3 Dr. Asha Tyagi 4 1. M.D., D.A., Professor and Head 2. M.D., D.N.B., Senior Resident 3. M.D., Reader 4. M.D., DNB, Lecturer Department of Anaesthesiology and Critical Care, U.C.M.S. and G.T.B. Hospital, Shahdara, Delhi, India - 110095 Correspond to : E-mail: aksethi@bol.net.in Introduction The syndrome of shock in humans is often the final pathway through which a variety of pathologic processes lead to cardiovascular failure and death. As such, shock is perhaps the most common and important problem with which the critical care physicians contend. It is one of the most common causes of death in the United States today

and, together with respiratory failure, accounts for most emergent intensive care unit (ICU) admissions. 1 The magnitude of the problem of shock is illustrated not only by absolute numbers of deaths but also in the high mortality percentages seen with various types of shock. History Despite recognition of a post traumatic syndrome by Greek physicians such as Hippocrates and Galen, the origin of the term shock is generally credited to the French surgeon Henri Francois Le Dran, who in 1737 defined the same as A treatise of reflections drawn from experience with gunshot wounds and coined the term choc to indicate a severe impact or jolt. 2 An inappropriate translation by the English physician Clare, in 1743, led to the introduction of the word shock to the English language to indicate the sudden deterioration of a patients condition when major trauma has occurred. 2 It was Edwin A. Moses, 3 who began to popularize the term, using it in his article

A practical treatise on shock after operations and injuries in 1867. Definition of Shock The definition of shock has evolved in parallel with our understanding of the phenomenon and many definitions of shock have appeared. 5 Until the late 1800s, the term shock was used to indicate the immediate response to massive trauma, without regard to a specific post trauma syndrome. Later, with the introduction of noninvasive blood pressure monitoring devices, most clinical definitions of shock added the requirement of arterial hypotension. 4 But current technology, which allows assessment of perfusion independent of arterial pressure, has shown that hypotension does not define shock. The emphasis in defining shock is on tissue perfusion in relation to cellular function. Thus, the most appropriate definition of shock is the state in which profound and wide spread reduction of effective perfusion leads first to reversible, and then, if prolonged, to irreversible cellular injury. 5

Classification A classification based on cardiovascular characteristics, which was initially proposed in 1972 by Hinshaw and Cox, 6 is the most accepted one amongst many others that have been given. It divides the syndrome into four major categories: hypovolemic, cardiogenic, extracardiac obstructive and distributive (Table 1). However, this is just an artificial separation and there is a frequent, considerable initial mixing and overlap within these categories. (i) Hypovolemic Shock It is characterized by a loss in circulatory volume, which results in decreased venous return, decreased filling of the cardiac chambers, and hence a decreased cardiac output which leads to increase in the systemic vascular resistance (SVR). The haemodynamic profile on monitoring of flow pressure variables shows low central venous pressure (CVP), a low pulmonary capillary wedge pressure (PCWP), low cardiac output (CO) and cardiac index (CI), and high SVR. The arterial blood pressure may be normal or low. (ii) Cardiogenic Shock

This is primarily dependent on poor pump function. Cardiogenic shock due to acute catastrophic failure of left ventricular pump function is characterized by high PCWP, low CO and CI, and generally a high SVR. (iii) Distributive or Vasogenic shock This type of shock is associated with not only poor vascular tone in the peripheral circulation but maldistribution of blood flow to organs within the body also. The CO varies, but is usually raised. A common haemodynamic profile is a low or normal PCWP, a high CO, a low arterial blood pressure, and a low SVR.346 INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003 Table - 1 : Classification of shock 6 HYPOVOLEMIC (oligemic) Hemorrhagic - Trauma - Gastrointestinal - Retroperitoneal Fluid depletion (nonhemorrhagic) - External fluid loss Dehydration Vomiting Diarrhea

Polyuria - Interstitial fluid redistribution Thermal injury Trauma Anaphylaxis Increased vascular capacitance (venodilatation) - Sepsis - Anaphylaxis - Toxins/Drugs CARDIOGENIC Myopathic - Myocardial infarction Left ventricle Right ventricle - Myocardial contusion (trauma) - Myocarditis - Cardiomyopathy - Post ischemic myocardial stunning - Septic myocardial depression - Pharmacologic Anthracycline cardiotoxicity Calcium channel blockers Mechanical - Valvular failure Regurgitant

Obstructive - Hypertropic cardiomyopathy - Ventricular septal defect Arrhythmic - Bradycardia Sinus (e.g., vagal syncope) Atrioventricular blocks - Tachycardia Supraventricular Ventricular EXTRACARDIAC OBSTRUCTIVE Impaired diastolic filling (decreased ventricular preload) - Direct venous obstruction (vena cava) Intrathoracic obstructive tumors - Increased intrathoracic pressure Tension pneumothorax Mechanical ventilation (with positive end-expiratory pressure [PEEP], autoPEEP or volume depletion) Asthma (with auto PEEP) - Decreased cardiac compliance Constrictive pericarditis Cardiac tamponade Acute Post-MI free wall rupture Traumatic

Hemorrhagic Chronic Malignant Uremic Idiopathic Impaired systolic contraction (increased ventricular afterload) - Right ventricle Pulmonary embolus (massive) Acute pulmonary hypertension - Left Ventricle Saddle embolus Aortic dissection DISTRIBUTIVE Septic (bacterial, fungal, viral, rickettsial) Toxic shock syndrome Anaphylactic, anaphylactoid Neurogenic (spinal shock) Endocrinologic Adrenal crisis Toxic (e.g., nitroprusside, bretyllium) (iv) Extracardiac obstructive shock It is associated with a physical impairment to adequate forward circulatory flow involving mechanisms different than primary myocardial or valvular dysfunction. Several hemodynamic patterns may be

observed, depending on the cause, from frank decrease in filling pressures (as in mediastinal compressions of great veins); to trends towards equalization of pressures in the case of cardiac tamponade; or to markedly increased right ventricular filling pressures with low PCWP in the case of pulmonary embolism. Cardiac output is usually decreased with increased SVR. Pathophysiology Shocks of all form involve common cellular metabolic processes that typically end in cell injury, organ failure and death. 7 The pathogenesis of shock involves multiple interrelated factors including (a) cellular ischemia, (b) circulating or local inflammatory mediators, and (c) free radical injury. (a) Ineffective perfusion leading to cellular ischemia plays a major role in cellular injury in most forms of shock. Hypoperfusion decreases the delivery of nutrients to the cells leading to diminished ATP production. 8 Essential ATP dependent intracellular metabolic processes that may be affected include

maintenance of transmembrane potential, mitochondrial function 9 and other energy-dependent enzyme reactions. Liver and kidney are particularly sensitive as intracellular levels of ATP fall and ATPdependent processes are impaired. 8,10-13 Lysosomal disruption is the point of irreparable cell damage analogous to clinical irreversibility. Worsening of shock, organ failure, and death may result. (b) The effect of inflammatory mediators on cellular metabolism is of prime importance in organ dysfunction resulting from sepsis and septic shock and also hemorrhagic shock associated with extensive trauma. 14,18 Generally, it is the endotoxin from gram negative bacteria that triggers the inflammatory cascade but bacterial antigens and cell injury it self can also initiate the cascade. Macrophage production of cytokines such as TNF-a and IL-1b appear to be the prime mediators. 19 Other substances involved in

the inflammatory process include IL-2, IL-6, interferon-a, endothelin-1, leukotrienes, thromboxanes, prostaglandins and complement fragments C3a and C5a . 19,20 Two other mediators, circulating myocardial depressant substance and nitric oxide have a role to play in septic shock. 23,24,25SETHI, SHARMA, MOHTA, TYAGI : SHOCK 347 (c) Free radical injury induced by reperfusion or neutrophil activity is another mechanism by which cell and organs suffer a damage. 26,27 Tissue ischemia leads to accumulation of adenosine, inosine and hypoxanthine. 28 With resuscutation, reperfusion of ischemic areas occurs. The availability of O2 generates superoxide (O2 ) by xanthine oxidase which is

converted to hydrogen peroxide (H2 O2 ) which further reacts to produce the highly reactive tissue damaging hydroxyl radicals. These inturn interact with critical cell targets resulting in cell lysis and tissue injury. Oxidant activity, directly and through endothelial damage attracts and activates neutrophils causing amplification of superoxide generation and further tissue damage due to neutrophil protease release. 27 Microvascular function in shock Microvessels (100-150mm diameter) is one of the key determinants of appropriate tissue perfusion during shock. Adequate cardiac output as well as normal local and systemic microvascular function ensure that specific tissues are effectively perfused. Distribution of cardiac output involves local intrinsic autoregulation and extrinsic regulation mediated by autonomic tone and humoral factors. Blood flow to individual organs may be affected by system wide changes in microarteriolar tone or by local alteration in metabolic activity. It is the precapillary arterioles and precapillary and postcapillary sphincters that are responsible for these tasks. During both irreversible hemorrhagic and septic

shock, peripheral vascular failure results. The potential mechanisms are (a) tissue acidosis 29 (b) catecholamine depletion and mediator related vascular resistance to catecholamine 30,33 (c) release of arachidonic acid metabolites 34-36 (d) nitric oxide generation 23,37,38 and (e) decreased sympathetic tone due to altered central nervous system (CNS) perfusion. 39 Other microvascular pathologic processes occurring in shock include disruption of integrity of endothelial cell barrier leading to loss of plasma proteins, decrease in plasma oncotic pressure, interstitial edema and fall in circulating volumel. 40,41 In addition, there is microvascular clotting and microthrombi leading to further inadequate distribution of perfusion within tissue. 42,43 Compensatory Responses to Shock

With the onset of hemodynamic dysfunction, homeostatic compensatory mechanisms engage to maintain adequate tissue perfusion. At this stage, signs and symptoms of hemodynamic stress may be apparent (i.e., tachycardia, decreased urine output) but overt evidence of shock (i.e., hypotension, altered sensorium, metabolic acidosis) are absent. All compensatory responses to shock, whether hemodynamic, metabolic or biochemical, support oxygen delivery to vital organs. These responses are similar for varying classes of shock and are divided into four categories (Table 2): (a) Maintenance of mean circulatory pressure (b) Maximizing cardiac function (c) Redistributing perfusion to vital organs (d) Optimizing unloading of oxygen at tissues Table - 2 : Cardiovascular/Metabolic compensatory responses to shock 5 Maintain Mean Circulatory Pressure (venous pressure) Volume - Fluid redistribution to vascular space From interstitium (Starling effect) From intracellular space (Osmotic effect) - Decreased renal fluid losses Decreased glomerular filtration rate (GFR)

Increased aldosterone Increased vasopressin Pressure - Decreased venous capacitance Increased sympathetic activity Increased circulating (adrenal) epinephrine Increased angiotensin Increased vasopressin Maximize Cardiac Performance - Increased contractility Sympathetic stimulation Adrenal stimulation Redistribution of Perfusion - Extrinsic regulation of systemic arterial tone - Dominant autoregulation of vital organs (heart, brain) Optimize Oxygen Unloading - Increased RBC 2, 3 DPG - Tissue acidosis - Pyrexia - Decreased tissue PO2 Mean circulatory pressure (and venous return) is sustained in early shock not only by sympathetic activation 44,45 causing precapillary vasoconstriction but also

by decrease in capillary hydrostatic pressure causing influx of interstitial fluid into the vascular compartment. 46 The intravascular volume may also be supported by the osmotic activity of glucose generated by glycogenolysis. 47 Intravascular volume is maintained by decreasing renal fluid looses and by release of rennin from juxtaglomerular apparatus. 48 Rennin converts angiotensinogen into angiotensin I which is further metabolized to angiotensin II 49 which causes aldosterone release. This in turn, increases sodium reabsorption in the distal tubules of the kidney. Angiotensin II is also a potent vasocontrictor particularly on mesenteric vessels and increases sympathetic348 INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003 out flow and adrenal epinephrine release. 49,50 Vasopressin released also causes water retention and vasoconstriction particularly of the splanchnic circulation. 51 Cardiac functions

are augmented by local release of norepinephrine by sympathetic nerves and systemic release of epinephrine, which stimulate cardiac a and b adrenergic receptors. During shock, increased sympathetic vasoconstrictor tone, systemic release of epinephrine from the adrenals, vasopressin and angiotensin II cause vasocontriction in all sensitive vascular beds, including skin, skeletal muscle, kidney and splanchnic organs. The vascular supply of the brain and heart is spared causing effective redistribution of flow to these vital organs. 44,45 Tissue ischemia results in local acidemia, which causes a decreased affinity between oxygen and haemoglobin. 56,57 Also, systemic alkalemia due to respiratory alkalosis leads to rapid increases of erythrocytes 2,3 diphosphoglycerate (DPG). Both of these cause rightward shift of oxyhaemolobin dissociation curve. Effect of shock on various organ systems (Table 3) (1) Brain - Though CNS neurons are extremely sensitive to ischemia, the vascular supply is highly resistant to extrinsic regulatory mechanisms. Patients without a primary cerebrovascular impairment, support their cerebral function well until the mean arterial pressure

falls below approximately 50-60 mmHg. 58,59 At this point, irreversible ischemic injury may occur to the most sensitive areas of the brain i.e., cerebral cortex and water shed areas of the spinal cord. 58,59 Before such injury, an altered level of consciousness varying from confusion to unconsciousness may be seen depending on the degree of perfusion deficit. El e c t r o e n c e p h a l o g r a p h i c ( E EG) r e c o r d i n g s demonstrate non-specific changes compatible with encephalopathy. (2) Heart - The major clinically apparent manifestations of shock result from sympatho adrenal stimulation. Heart rate is usually increased except in case of severe haemorrhage where vagally mediated paradoxical bradycardia may occur. 60,61 In addition, catecholamine driven supraventricular tachycardia and ventricular ectopy with ichaemic ECG changes (in patients predisposed to myocardia ischaemia) may be seen. Systemic hypotension compromises coronary

perfusion leading to overt ischemia in high risk patients. 62 Circulating myocardial depressant factors contribute to myocardial depression in septic 21,22 and haemorrhagic shock. Unless shock is of cardiac origin, the heart usually plays a participatory role in which it is unable to compensate fully for arterial hypotension caused by hypovolemia, vasodilatation, or other factors. 63 Table - 3 : Organ system dysfunction in shock 5 Central Nervous System Encephalopathy (ischemic or septic) Cortical necrosis Heart Tachycardia, Bradycardia, Supraventricular tachycardia, Ventricular ectopy, Myocardial depression Pulmonary Acute respiratory failure, Adult respiratory distress syndrome Kidney Prerenal failure, Acute tubular necrosis Gastro-Intestinal Ileus Erosive gastritis, Pancreatitis, Acalculous cholecystitis, Colonic submucosal hemorrhage, Transluminal translocation of bacteria/antigens

Liver Ischemic hepatitisShock liver intrahepatic cholestasis Hematologic Disseminated intravascular coagulation, Dilutional thrombocytopenia Metabolic Hyperglycemia, Glycogenolysis, Gluconeogenesis, Hypoglycemia (late), Hypertriglyceridemia Immune System Gut barrier function depression, Cellular immune depression, Humoral immune depression (3) Respiratory system - Increased respiratory drive resulting from peripheral stimulation of pulmonary J receptors and carotid body chemoreceptors, as well as hypo-perfusion of the medullary respiratory center results in increased minute volume (tachypnea, hyperpnea), hypocapnia and primary respiratory alkalosis. 64 With increased minute volume and decreased cardiac output, the V/Q ratio is increased. Coupled with an increased workload, respiratory and diaphragmatic muscle impairment caused by hypoperfusion may lead to early respiratory failure. 65,66 If shock is not promptly reversed and the initiating condition controlled adult respiratory distress syndrome (ARDS) may develop.

(4) Kidney - Oliguria, as defined by a urinary output less than 0.5 mlkg -1 hour is a cardinal manifestation of shock. Sympathetic stimulation, circulating catecholamines, angiotensin, and locally produced prostaglandin contribute to afferent arteriolar vasoconstriction and the redistribution of blood flow away from cortex to the medulla. 63,67,68 The net effect is a decreased glomerular filtration rate. The three pathologic changes seen are (a) tubular necrosis (b) tubular obstruction by casts or debris and (c) tubular epithelial damage. It is because of these pathologic changes that restoration of normal hemodynamic function does not often lead to an immediate improvement in renal function. Urine produced during shock often reflects the pathophysiologic changes occurring in kidney. IfSETHI, SHARMA, MOHTA, TYAGI : SHOCK 349 reflex vasoconstricting mechanisms predominate (i.e., hypovolemic and cardiogenic shock), the urine has an osmolality in excess of 450 mosmlL -1 , sodium

concentration of less than 20 mmolL -1 , fractional excretion of sodium less than 1% and a urine to plasma creatinine ratio of over 40. However, with acute tubular necrosis the osmolality of urine decreases to less than 350 mosmlL -1 , sodium concentration gets over 40 mmolL -1 with fractional excretion of sodium of over 2% and a urine to plasma creatinine ratio of less than 20. 69 (5) Gastrointestinal - Typical clinical manifestations of hypoper fusion, sympathet ic st imulat ion and inflammatory injury associated with shock includes ileus, erosive gastritis, pancreatitis, acalculous cholecystitis and colonic submucosal hemorrhage. 70,71,72 Also, enteric bacteria and antigens translocate from the gut lumen into the systemic circulation during gut ischemia causing irreversible shock. 73,74

(6) Liver - Centrilobular injury with mild increases of transaminases and lactate dehydrogenase usually peaks within 1-3 days of ischemic insult and resolves over 3-10 days. Shock liver associated with massive ischemic necrosis and a major elevation of transaminases is atypical in the absence of extensive hepatocellular disease. 75 In both, only mild increases in bilirubin and alkaline phosphatase is seen in early shock. Though, the clnical manifestations are not apparent in early stages of shock, as the organ participates in the release of acute phase reactants but synthetic functions may be impaired with decreased generation of prealbumin, albumin and hepatic coagulation factors. 76 Biliary stasis with increased bilirubin uptake and alkaline phosphatase may be seen after hemodynamic resolution of the shock. (7) Hematologic - Disseminated intravascular coagulation (DIC) characterized by microangiopathic hemolysis, consumptive thrombocytopenia, consumptive coagulopathy and microthrombi with tissue injury is

seen commonly in sept ic shock. Di lut ional thrombocytopenia after volume replacement is associated with hemorrhagic shock. 77 (8) Metabolic - In early shock, sympathoadrenal activity is enhanced causing increased release of adreno corticotrophic hormones (ACTH), glucocorticolds and glucagons and decreased release of insulin. 78 Also, glycogenolysis and gluconeogensis contribute to hyperglycemia. Later, glycogen depletion or failure of hepatic glucose synthesis leads to hypoglycemia. 79 Fatty acid initially increase but later with hypoperfusion of adipose containing peripheral tissue, levels fall. 80 Increased catecholamines, glucocorticoids and glucagon increase protein catabolism causing negative nitrogen balance. 78,80 Catecholamine stimulation and reduced lipoprotein lipase expression also causes hypertriglyceridemia. 78,81

(9) Immune system - Compromised immune functions are due to injury to barrier mucosa especially of the gut; parenchymal tissue injury from associated trauma, or free radical injury; and direct ischemic or mediator induced dysfunction of cellular and humoral immune system. 82,83 Diagnostic Approach and Evaluation Shock is an end-stage of a continuum of progressive physiologic derangements. It is imperative, therefore, that clinicians recognize the early stages of shock at a time when it is more responsive to treatment. A monitored physiologic approach to therapy provides the best opportunity for successful outcome and avoidance of organ dysfunction. Not only the initial resuscitative technique but continuous evaluation of the patients condition is important. (Table 4) Table - 4 : General Approach to Shock: Initial Diagnosis and Evaluation 5 Clinical Tachycardia, tachypnea, cyanosis, oliguria, (primary diagnosis) encephalopathy (confusion), peripheral hypoperfusion (mottled extremities), hypotension (systolic blood pressure < 90 mm Hg; mean arterial pressure <65 mm Hg)

Laboratory Hemoglobin, WBC, platelets (confirmatory) PT/PTT Electrolytes, arterial blood gases Ca, MgBUN, creatinine Serum lactate ECG Monitoring Continuous ECG and respiratory monitors Arterial pressure catheter Central venous pressure monitor (uncomplicated shock) Pulmonary artery flotation catheter Cardiac output Pulmonary wedge pressure Mixed venous oxygen saturation (intermittent or continuous)* Oxygen delivery (Do 2 ) and oxygen consumption (VO2 )* Oximetry* Transcutaneous oxygen tension* Gastric intramucosal pH* Echocardiogram (functional assessment)* Imaging Chest radiograph Radiographs of abdomen*

Computerized axial tomogram (CT scan), abdomen or chest* Echocardiogram (anatomic assessment)* Pulmonary perfusion scan*350 INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003 Clinical presentation This varies with the previous level of organ function, compensatory mechanisms, severity of organ dysfunctions and the cause of shock syndrome. Impending shock is characterized by the typical compensatory response to cardiovascular stress. Tachycardia, tachypnea and oliguria are the hall mark. Cool extremities are seen in hypodynamic shock. With progression, blood pressure falls and frank hypotension (MAP<60-65mmHg) ensues. With further progression, anuria, mottled, dusky extremities and altered sensorium occurs. (Table 5) Table - 5 : Clinical Recognition of Shock 5 ORGAN SYMPTOM CAUSES SYSTEM OR SIGN CNS Mental status changes Decreased Cerebral perfusion Pinpoint pupils Narcotic overdose Circulatory Tachycardia Adrenergic stimulation, Heart depressed contractility Other dysrhythmias Coronary ischemia Hypotension Depressed contractility

secondary to ischemia or MDFs, right ventricular failure Systemic New murmurs Valvular dysfunction, Hypotension VSDDecreased SVR, decreased Decreased JVP venous return Hypovolemia, decreased venous return Increased JVP Right heart failure Disparate peripheral pulses Aortic dissection Respiratory Tachypnea Pulmonary edema, respiratory muscle fatigue, sepsis, acidosis Cyanosis Hypoxemia Renal Oliguria Decreased perfusion, afferent arteriolar vasoconstriction Skin Cool, clammy Vasoconstriction, sympathetic stimulation Other Lactic acidosis Anaerobic metabolism, hepatic dysfunction Fever Infection Laboratory studies There are used not only for confirmation of diagnosis of shock but also to know the etiologic factors. Initial laboratory tests should include a complete chemistry profile with serum electrolytes, creatinine, blood urea nitrogen (BUN), liver function tests, calcium, magnesium and

phosphate levels, a complete blood count and differential; a platlet count; serum lactate levels; prothrombin and activated partial thromboplastin times, urinalysis with a detailed sediment analysis, serum amylase level; and arterial blood gases (ABG). Leucocyte count is frequently elevated early in shock caused by demargination of neutrophils. Leucopenia is found in sepsis and late shock. Haemoglobin level varies with the type of shock. Stress of circulatory shock increases platlet count initially but with proression thrombocytopenia occurs. BUN and creatnine rarely change after the acute creatinine onset of shock, even if renal injury is present. ABG determines the adequacy of oxygenation and acid base status. Serial serum lactate levels are used in the assessment of prognosis and levels of >2meqL -1 represent tissue ischemia. Pregnancy test should be performed in all females of child bearing age. A 12 lead ECG is critical for diagnosis of ischemic cardiac injury either as a primary cause of cardiogenic shock or secondary to hypotension associated with other shocks. Chest radiograph is also a must. Other studies should be considered in specific conditions and may include blood, sputum and urine gram stains and

cultures in all cases of suspected sepsis. More detailed imaging studies like CT scans, abdominal radiographs or ultrasound, surface or transesophageal echocardiograms 84,85 ventilation/perfusion scan, angiograms and cardiac isoenzymes 86 may be ordered for as and when required. Typing and crossmatching for several units of packed RBCs and fresh frozen plasma should be asked for when a significant blood loss is observed, anticipated, or suspected. Invasive hemodynamic monitoring Arterial pressure catheter is a must for all patient suspected of having circulatory shock. Marked peripheral vasoconstriction may make the assessment of blood pressure by manual sphygmomanometry or automated noninvasive oscillometric technique inaccurate. 87 Also, continuous monitoring of the rapidly changing hemodynamic status of unstable patients and access for ABG samples is available with arterial catheter in place. Central venous pressure monitoring is not an accurate means of monitoring volume resuscitation and

should be used only as a rough guide. An initially low CVP (i.e., less than 5mmHg) may indicate hypovolemia and a CVP more than 15mmHg with an absent Y descent suggests cardiac tamponade in the appropriate clinical setting. As a rule, CVP monitoring is inadequate for the hemodynamic assessment of critically ill patients and also it does not accurately estimate left ventricular preload in critically ill patients. 88,89SETHI, SHARMA, MOHTA, TYAGI : SHOCK 351 Flow directed ballon tipped pulmonary artery catheter with thermodilution cardiac output determination capability have become the standard practice for the hemodynamic assessment of circulatory shock. 90,91,92 Continuous monitoring of central venous and pulmonary artery waveforms and pressures is also provided by them. It is also useful for etiologic classification of shock, determination of optimal management and response to the therapy. Mixed venous oxygen saturation provides an assessment of adequacy of resuscitation of low output states before the presence of anaerobic metabolism. Normal SVo2 falls within 65%-75% range. SVo2 rises with increases of perfusion above requirements and falls, with increasing oxygen extraction ratio, as perfusion become inadequate.

Oxygen delivery and oxygen consumption variables can also be determined using pulmonary artery catheterderived data. But, the utility of this data is controversial when applied to individual patients. Recent modification to the standard pulmonary artery floatation catheter allows continuous monitoring of SVo2 or determination of right ventricular ejection fractions and volumes though they have no defined role at this time in clinical shock management. Ancillary monitoring techniques Pulse oximetry has a limited use in the acute management of circulatory shock and may be more helpful in the post resuscitation monitoring. Transcutaneous and transconjunctival oxygen tension measurements are newer noninvasive techniques for determining tissue oxygen tensions. 93,93,95 Gastric mucosal pH is also a noninvasive method for assessment of adequacy of tissue oxygenation/ perfusion. It correlates well with systemic and organ oxygen consumption, organ failure and outcome in critically ill patients. 96,97 Normalization of gastric mucosal pH is also one of the target during resuscitation of circulatory shock. Echocardiography in the ICU not only detects the anatomic

lesions but also allows direct measurement of cardiac output, stroke volume, preload, systolic contractility, diastolic function and regional motion abnormalities. 99 There are other promising noninvasive monitoring devices i.e, near-infrared spectroscopy to detect oxygen availability and utilization at tissue level and thoracic electrical bioimpedance for continuous cardiac output measurements. These could be used with high risk patients to detect compensated states , before cl inical hemodynamic instability is evident. But, more studies and refinement are necessary before the golden standard (pulmonary artery catheter with a thermistor tip) can be challenged. 100,101-105 Management and Therapy Patients in shock should be managed in ICU with continuous ECG monitoring and close nursing support. Invasive hemodynamic monitoring with arterial and pulmonary artery catheters should be instituted in those indicated i.e., patients in whom etiologic diagnosis is in doubt, whose hemodynamic instability does not quickly resolve with intravenous fluids etc., laboratory tests as mentioned before should be performed the earliest possible. Management of shock can be divided into specific therapy

for triggering injury and general therapy of the shock syndrome. (Table 6) Table - 6 : General approach to shock: Immediate goals 5 Hemodynamic MAP>60-65 mm Hg (higher in the presence of coronary artery disease or chronic hypertension) PWP = 12 to 18 mm Hg (may be higher for cardiogenic shock) CI>2.1 Lmin -1 m-2 for cardiogenic and obstructive shock>3.0 to 3.5 Lmin -1 m-2 for septic and resuscitated traumatic/hemorrhagic shock. Optimization of Hemoglobin >10 gdL -1 oxygen delivery Arterial saturation>92% Svo 2 >60% Normalization of serum lactate (to <2.2 meqL -1 )

Reverse organ Reverse encephalopathy system Maintain urine output >0.5 mlkg -1 hr -1 dysfunction Aims - The basic goal of circulatory shock therapy is the restoration of effective perfusion to vital organs and tissues before the onset of cellular injury. This in turn depends on cardiac index (CI) and mean blood pressure. The first specific resuscitative aim should be support of blood pressure greater than 60-65 mmHg in a baseline normotensive patient. The second aim, maintainence of CI greater than 2.1Lmin -1 m-2 for cardiogenic and obstructive shock and greater than 3.0-3.5 Lmin -1 m2 for septic and resuscitated hemorrhagic shock should be then looked after. Finally, maintaining perfusion sufficiently high to keep arterial lactate concentration <2.2 meqL -1

avoids anaerobic metabolism. The concept that augmenting O2 delivery (Do 2 ) to supranormal levels increase oxygen consumption and thereby, decrease organ failure and mortality remains controversial. More recent investigations have cast doubts on this therapeutic approach of augmenting Do 2 . 106-109 (a) Airway management and mechanical ventilation A critical first step in the treatment of shock is to ensure adequate alveolar ventilation and oxygenation. Most patients with the fully developed shock syndrome require tracheal intubation and mechanical ventilatory352 INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003 support, even if acute respiratory failure has not yet occurred. Improvement may occur for several reasons. Mechanical ventilation allows blood flow to be redistributed, tends to reverse lactic acidosis and supports the patient until other therapeutic measures can be effective. Tracheal intubation also is indicated if mental status changes make airway unprotected or

for inadequate respiratory compensation for metabolic acidosis. 110 Initial guidelines include using calculated tidal volumes in the order of 7-10 mlkg -1 of lean body mass, an O2 concentration that results in arterial saturation not less than 92%, adequate ventilator rate and sedation to minimize the work of breathing. 63 Positive-pressure ventilation and PEEP may produce further hemodynamic compromise if volume status of the patient is not maintained. PEEP may also be desirable in patients with ARDS or pulmonary edema to ensure adequate oxygenation. (b) Acid base Balance The previous standard practice of administering bicarbonate to patients with shock and lactic acidosis has been revised. Recent evidence has demonstrated that metabolic acidosis of the plasma may infact be protective in shock states and that bicarbonate administration may transiently decrease intracellular and cerebrospinal fluid PH.

111 The mechanism being production of CO2 as a product of the bicarbonate buffering of hydrogen ion and the rapid diffusion of this non ionized CO2 across cellular membranes. This paradoxical intracellular acidosis hinders brain and cardiac functions. Thus, the optimal approach to the management of lactic acidosis is to improve organ and systemic perfusion so that anaerobic metabolisms is limited and the liver as well as kidney can clear the accumulated lactate. If not effective, it has been suggested to restrict the use of sodium bicarbonate to situations with PH <7.1-7.15. (c) Fluids Common to all etiologies of hemodynamic instability and shock is the need to provide optimal intravascular volume to ensure adequacy of preload. Thus, it is appropriate to begin fluid administration in all shock patients who lack signs of pulmonary edema and left ventricular overload. Substantial controversy exists regarding the appropriate use of crystalloid and colloid fluids for resuscitation. 112-114

Several metaanalyses determined that there is no benefit and even perhaps mild increased mortality associated with the use of colloids instead of crystalloids for fluid resuscitation. 115 Thus, given the much higher cost of colloids, resuscitation of shock should generally focus on crystalloid solutions unless speed of resuscitation is paramount (i.e., acute major trauma or massive hemorrhage). What is most important when either type of fluid is used is to determine responses to these fluid challenges. Optimal therapy generally means administering the quantity of fluid that maximizes Do 2 while avoiding left ventricular overload and pulmonary edema. Also, sufficient preload should be there before or during institution of pharmacologic therapy for hypoperfusion. (d) Vasopressor agents The term pressor refers to any substance that raises BP. These agents are divided into 3 categories: (i) lonotropes/chronotropes (i.e., drugs that increase cardiac output (CO) by increasing cardiac contractility and heart rate); (ii) vasoconstrictors (i.e., agents that

raise BP by increasing systemic vascular resistance); and (iii) mixed pressor agents (i.e., drugs that act through both mechanism). (i) Ionotropic/chronotropic agents Dobutamine hydrochloride, a synthetic b 1 ,b 2 receptor agonist is often used for ionotropic support in cardiogenic shock. It increase myocardial contractility and CO, reduces afterload through peripheral vasodilatation and decreases left ventricular filling pressures with improvement in diastolic coronary blood flow. It also prevents increase in infarct size in patients with acute myocardial infarction by improved collateral blood flow and balance between oxygen supply and demand. 116,117 Because of b 2 mediated vasodilatation caution should be observed if it administered to hypotensive patients, especially with coexistent hypovolemia.

Milrinone lactate, a selective phosphodiesterase III inhibitor increases ionotropy and decreases systemic vascular resistance by preventing the degradation of cyclic adenosine monophosphate. The hemodynamic effects are similar to those of dobutamine. Amrinone, is rarely used because of excessive vasodilatation and thrombocytopenia following long term use. It may be useful for synergy in patients already taking a-agonists and for patients receiving b-blocking agents. The most accepted use of these agents in the ICU in the management of congestive heart failure, cardiogenic shock and post-cardiopulmonary by pass myocardial dysfunction.SETHI, SHARMA, MOHTA, TYAGI : SHOCK 353 Dopexamine, a synthetic catecholamine, augments cardiac performance through both b 2 mediated afterload reduction and baroreceptor reflex mediated ionotropy. Also, added benefit is its dopaminergic mediated increase in renal blood flow. Isoproterenol hydrochloride, a pure b receptor agonist produces CO augmentation by increasing both HR and contractility. Dysrythmias and increased myocardial oxygen

requirement limit the use. Digitatis has limited use in treating acute states of hypoperfusion due to its slow onset of action and lower potency. (ii) Vasoconstrictor agents Phenylephrine is a pure adrenergic agonist. It causes vasoconstriction thereby increasing BP, generally decreasing CO and often reflex slowing of HR. It should be used as a first line agent in neurogenic shock. It can also be useful in patients who, despite maximal fluid and ionotropic support, remain hypotensive with evidence of organ hypo perfusion. Pure vasoconstrictors may compromise flow and perfusion, thus attention to renal function, acid-base balance, serum lactate and Do 2 is imperative. Vasopressin is used as an alternative therapy for vasodilator shock especially where a stimulation does not produce a satisfactory vasoconstrictor response. 118,119 Most studies have used doses between 0.01 and 0.1U per minute. 120,121

Other vasoconstrictors are nor-epinephrine and bitartrate. (iii) Mixed Pressor Agents Dopamine, a precursor of norepinephrine, is commonly used as an initial pressor agent, acting at several receptors in a dose related manner. It can be titrated towards achieving different aims of therapy : dopaminergic effects at less than 4-5 mgkg -1 min -1 (e.g., vasodilatation of renal and splanchnic vascular beds), b effect at 5-10 mgkg -1 min -1 (e.g., augmentation of cardiac contractility and HR) and a effects at more than 10 mgkg -1 min -1

(e.g., vasoconstriction). Debate continues, however, as to whether dopamine truly improves renal function or merely increases urine output through diuretic effect. There has been a decreased enthusiasm for its routine use to protect the kidneys from hypoperfusion insults or as a means to promote urine output in post hypoperfusion oliguria. 122 However, at dose of 2-3 mgkg -1 min -1 it can reverse vasoconstrictor induced increases in renal vascular resistance during vasoconstrictor infusion. 123,124,125 Norepinephrine exerts both powerful ionotropic (cardiac a and b 1 adrenoreceptors) and peripheral vasoconstriction effects (a adrenoceptors). It can be used for persistent hypotension despite high dose dopamine during septic and obstructive

shock. 126 It may also improve splanchnic oxygen dynamics in patients with sepsis. 127 Epinephrine is occasionally used when other ionotropes/vasopressors have failed to support blood pressure and/or cardiac output in circulatory shock. 128 It is the first line agent for management of anaphylactic shock. All currently used vasopressors agents ultimately produce their effects by increasing intracellular ionized calcium concentration. Thus normal ionized calcium concentration should be maintained in patients who are on vasopressor support. (e) Vasodilator agents These drugs reduce afterload and improve CO in acute and chronic ventricular failure. For acute vasodilatation and preload reduction, nitroglycerin is the agent of choice; for afterload reduction, sodium nitroprusside, hydralazine hydrochloride, anggiotensin converting enzyme inhibitors and fenoldopam are

preferable. Patients with right-sided heart failure may benefit from pulmonary vasodilators i.e., prostacyclin, prostaglandin E 1 and inhaled nitric oxide. ( f ) Steroids Prospective, double-blind, randomized, multicenter studies have demonstrated no benefit of steroid administration in hyperdynamic/septic shock. Thus, the practice of routine administration of high dose s t e r o i d s wa s a b a n d o n e d . S t r e s s d o s e s o f glucocorticoids are appropriate for treating shock when it is associated with adrenal insufficiency, hypothyroidism, in patients with impaired adrenal pituitary axis, or in those who require steroids for treatment of an underlying immunologic disease (e.g., vasculitis). Conversely, steroids are relatively contraindicated in patients with cardiogenic shock as they alter the healing process of the myocardium and predispose to myocardial rupture. 133 But recent reports also suggest a decrease in the endogenous production of stress steroids in sepsis, causing vasopressor dependence and failure to respond to therapy.

131,132 Administration of 100 mg of hydrocortisone 8 hourly indicates benefit. The mechanism for benefit may be354 INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003 reversal of catecholamine receptor down regulation or prevention of inflammatory mediated induction of nitric oxide synthase. Patients of shock, who require increasing doses of vasopressors or do not respond within 24 hrs of therapy may be administered steroids. However, the topic still remains controversial. Experimental Therapies A number of promising new agents have begun to undergo experimental and clinical study for the treatment of ischemia and circulatory shock. The release of proinflammatory cytokines is one of the pathway to MODS in shock. 134 The use of receptor and enzymatic blockers as well as immunotherapy to minize the effect of these agents is of little use. 135 Antibodies to endotoxin, platlet activating factor, tumor necrosis factor, receptor blockers to interleukin-1, administration of the anti-inflammatory cytokine interleukin1, and inhibition of nitric oxide synthase have not been effective in randomized studies of patients

with SIRS. 136-140 Magnesium chloride complexed adenosine triphosphate (ATP-Mgcl 2 ), 141 pentoxifylline, 142 oxygen free radical scavengers 143 (i.e., superoxide dismutase, allopurinol), calcium channel blockers, 144,145 haemoglobin based blood substitutes (i.e., diaspirin-linked hemoglobin, bovine hemoglobin) are being assessed in experimental hemorrhagic and septic shock models. 146,147 Studies of activated protein (APC) have supported its role as an endogenous anti-inflammatory compound that also blocks thrombin induced microcoagulation. 148 APC

levels are decreased in 85% of patients with sepsis and SIRS. The recommendation is for the early (within 24 hours of diagnosis) administration to all patients with three of four indices of SIRS, known or suspected infection, and single-organ dysfunction. Other agents that may hold some promise for the management of circulatory shock of varying causes include novel buffers of acidemia (i.e., disodium carbonate/sodium bicarbonate), 149 bacteriocidal increasing permeability protein (BPI) 150 and chloroquine. 151 Recently, terlipressin, a long acting vasopressin analogue has also been studied in cases with septic shock who did not respond to corticosteroids and methylene blue. This agent has been suggested to be an effective rescue therapy and was able to restore blood pressure in patients with catecholamine-resistant septic shock without obvious complications including rebound hypotension as has been reported with vasopressin. 152 Summary

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151. Ertel W, Morrison MH, Ayala A, et al. Chloroquine attenuates h emo r r h a g i c s h o c k i n d u c e d immu n o s u p p r e s s i o n a n d decreases susceptibility to sepsis. Arch Surg 1992; 127: 70. 152. Alastair OBrien, Lucie Clapp, Mervyn Singer. Terlipressin for noreplnephrine-resistant septic shock. Lancet 2002; 359: 1209-1210. Election to the Governing Council ISA-2004 will be held at the Conference venue of ISACON 2003, on 28.12.2003 at Bhuvaneshwar. The vacancies open for the year - 2004 are: (a) President - (one post) (b) Vice-President - (one post) (c) Editor - (one post) (d) Governing Council Members - (3 posts) The rules and regulations regarding the election to the Governing Council of ISA are as per the Constitution of ISA (Article No.VII) published in 2002. Nomination in the proper format may be forwarded to the Secretary ISA, at Societys office by registered post/courier/in person, on or before 27 th November 2003. Secretary ISA (National) ISA NEWS : Election - ISA - 2004 - Vaccancies - Notification INDIAN SOCIETY OF ANAESTHESIOLOGISTS : Elections - 2003 PROFORMA (For Nomination of Office - Bearers to the Governing Council ISA National) I propose the name of Dr...................................................................

of .................................City Branch/Direct Member ............................ .....................as President / Vice President / Editor / Governing Council Member of Indian Society of Anaesthesiologists. Candidates Name & Qualification Address ISA No. Proposers Name Address ISA No. Signature I second the above proposal Seconders Name Address ISA No. Signature I give my consent to the above proposal Conference Attended: 1998 - Kathmandu 2001 - Ahmedabad 1999 - Cochin 2002 - Coimbatore 2000 - Nagpur Signature of the candidate Place: Date: $$