Treatment Continuous cardiac monitoring is essential, and multiple dose AC should be consid ered. Increasing arterial pH to \211 7.45 signi \201 cantly reduces the available free dr ug, and this may avoid TCA toxicity. Mild hyperventilation and 8.4% sodium bicarbonate in 5 0mmol aliquots achieves this strat- egy, and may improve outcome. Bicarbonate should prob- ably be given in all cases of QRS prolongation (even in the absence of metabolic acidosis), malignant arrhythmias, 443 CHAPTER 25.1 Management of acute poisoning hypotension or metabolic acidosis. If arrhythmias occur, avoid Class 1a agents; lidocaine m ay be best. Benzodiazepines are the drug of choice for sedation, treatment of seizures and prevention of the emergence of delirium. Barceloux DG, Bond GR, Krenzelok EP, et al. American Academy of Clinical Toxicology practic e guidelines on the methanol poison- ing. J Toxicol Clin Toxicol 2002; 40: 415 \200\22346. Buckley NA, Isbister GK, Stokes B, et al. Hyperbaric oxygen for carbon monoxide poisoning: a systematic review and critical analysis of the evidence. Toxicol Rev 2005; 24: 75 \200 \22392. Further reading American Academy of Clinical Toxicology; European Association of Poison Con trol Centers and Clinical Toxicologists. Position state- ment: gastric lavage. Clin Toxicol 1997; 35: 711 \200\2239. Chyka PA, Seger D, Krenzelok EP, et al. American Academy of Clinical Toxicology; European A ssociation of Poisons Centers and Clinical Toxicologists. Position paper: single-dose activ ated char- coal. Clin Toxicol 2005; 43: 61 \200\22387. American Academy of Clinical Toxicology; European Association of Poison Control Centers and Clinical Toxicologists. Position state- ment: whole bowel irrigation. Clin Toxicol 1997; 3 5: 753 \200\22362. Hall AP, Henry JA. Acute toxic effects of \200\230Ecstasy \200\231 (MDMA) and related comp ounds: overview of pathophysiology and clinical management. Br J Anaesth 2006; 96: 678 \200 \22385. American Academy of Clinical Toxicology; European Association of Poison Control Centers and Clinical Toxicologists. Position state- ment and practice guidelines on the use of multi-d ose activated charcoal in the treatment of acute poisoning. Clin Toxicol 1999; 37: 731 \200 \22351. Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alka- linisation. J Toxicol Clin Toxicol 2004; 42: 1 \200\22326. Seger DL. Flumazenil \200\224treatment or toxin. J Toxicol Clin Toxicol 2004; 42: 209 \200\22316. American Academy of Clinical Toxicology and European Association of Poisons Centers and Cli nical Toxicologists. Position paper: ipe- cac syrup. J Toxicol Clin Toxicol 2004; 42: 133 \200\22343. This page intentionally left blank 445 Chapter 26 Shock Chapter contents Shock: de \201 nition and diagnosis 446 Hypovolaemic shock 450 Cardiogenic shock 452 Anaph ylactic shock 456 Septic shock: pathogenesis 458 446 D DE BACKER Shock: de \201 nition and diagnosis Shock, or acute circulatory failure, defines a state in which the delivery of oxygen and nu trients to the tissue is insufficient to meet basal metabolic needs, leading to tissue hypo xia, and, if persistent, to MOF and death. Shock results from tissue hypoperfusion and micr ocirculatory dysfunction, and should thus not be restricted to hypoten- sion. Although freq uent, hypotension is not mandatory for the diagnosis of shock. In the absence of hypotensio n, increased lactate levels may indicate tissue hypoper- fusion and can be used to diagnose shock (at least at its initiation). Obstructive shock Hypovolemic shock Cardiogenic shock Distributive shock Fig. 26.1.1 The four categories of shock. Clinical \201 ndings Hypotension Hypotension is de \201 ned by an SBP <90mm Hg or a MAP <65mm Hg, or requirement for vasopressor agents to maintain blood pressure above these leve ls. Identifying the type of shock is thus important as it helps to indicate what should be the target of the primary interven- tion. There may be some overlap between these presenta- tio ns, as a patient with distributive shock may also present hypovolaemia and myocardial depre ssion. These four pres- entations of shock cover multiple causes. Distributive shock includ es septic shock, anaphylactic shock, pancreati- tis and ischaemia \200\223reperfusion injur y. All these causes of distributive shock are characterized by a marked activation of in \202 ammatory processes leading to the release of vasoac- tive substances. Signs of perfusion alteration to the organs Alteration in mental state: confusion, agitatio n, sometimes coma. Oliguria: urine output <0.5ml/kg/h. Requires at least 1h to be diagnosed , and sometimes longer when the bladder is not catheterized. Skin vasoconstriction (clammy skin): may be absent in dis- tributive shock states. How to diagnose the type of shock Differentiation between the four categories of shock can be made using several haemodynamic monitoring tools, including a pulmonary artery catheter, cardiac echocardi- ography and pulse contour analysis. Whatever the tech- nique used, clas sification of shock relies on the determination of cardiac output and evaluation of intrava s- cular pressures or volumes (Fig. 26.1.2). Measurement of cardiac output is essential to discriminate between the different types of shock: cardiac output and oxygen delivery are d ecreased (hypodynamic shock) in hypovolaemic, cardiogenic and obstructive shock, while it m ay be preserved and even increased in distributive shock (hyperdynamic shock). To identify further the different components of hypody- namic shock, the determination of intravascular pressures (CVP) is essential: it is decreased in hypovolaemia, but increased in cardiogeni c and obstructive shock. Of note, hypovolaemia can complicate any type of shock. Echocardio graphy is mandatory to differentiate obstruc- tive from cardiogenic shock (even though some indexes can be inferred from the pulmonary artery catheter or measurements of intravascula r volumes with transpulmo- nary thermodilution) and to determine the exact cause of cardiog enic shock (contractility, valve disease). Biological signs Metabolic acidosis is due to excess of hydrogen ions due to ATP hydrolysis occurring during anaerobic metabo- lism. Hyperlactataemia also occurs in response to hypox ia. In the absence of oxygen, pyruvate cannot enter the Krebs cycle and lactate is produced in large amounts. Normal values are close to 1mEq/l; values >2.0 suggest tis- sue hypoxia, values >4.0 are associated with a mortality rate >50%. Of note hyperlactataemia may also o ccur in the presence of oxygen (increased aerobic glycolysis in response to in \202 ammato ry processes) or may re \202 ect past rather than ongoing tissue hypoxia when liver lactat e clearance is decreased. In the early phases of shock, hyperlactataemia is highly suggesti ve of tissue hypoxia; at later stages, hyperlactataemia should be interpreted more cautious ly. Signs of organ dysfunction: decreased PaO2, increased cre- atinine levels, hyperbilirub inaemia. Increased tissue to arterial PCO2 gradient. Tissue PCO2 can be estimated in the st omach and in the sublingual area. An increased gradient (>10mm Hg) suggests tissue hypop- e rfusion. A gradient >20mm Hg may be associated with tissue hypoxia. Classi \201 cation of shock Weil and Subin have classi \201 ed shock into four categories : hypovolaemic, cardiogenic, obstructive and distributive. In this categorization of shock, the circulation is divided into its four essential components (Fig. 26.1.1): \200 \200 \200 \200 The four types of shock Hypovolaemic shock Hypovolaemic shock is characterized by a profoun d reduc- tion in blood volume. It is the most common source of shock, and can be due either to bleeding (trauma, digestive hemorrhage or other causes of blood losses) or to decreased plasma volume (dehydration most commonly due to diarrhea or vomiting). Children are very s ensitive to dehydration. the vascular reservoir (hypovolaemic shock) the pump (cardiogenic shock) the conduits (obst ructive shock) distribution of blood \202 ow among and within the organs (distributive sh ock). 447 CHAPTER 26.1 Shock: de \201 nition and diagnosis Cardiac output Normal or elevated Low Elevated LV preload (high PAOP or Dilated LA/LV) Elevated RV preload (high CVP or RV dilation) Elevated LV and RV preload DISTRIBUTIVE SHOCK Low preload Cardiogenic shock global dysfunction Cardiogenic shock LV dysfunction Cardiogenic shock RV dysfunction Hypovolemic shock Obstructive shock (pulmonary embolism or hypertension) Obstructive shock (tamponade) Fig. 26.1.2 The diagnostic tree. (Fig. 26.1.2). Intravascular pressures can either be invasively measured (central venous an d pulmonary artery catheters) or estimated by echocardiography. Intra- vascular volumes can be estimated by echocardio- graphy and transpulmonary thermodilution. Of note, the latter cannot differentiate left and right ventricular volumes. The typical clinical presentation is a patient with hypoten- sion, skin vasoconstriction an d collapsed jugular veins. The key haemodynamic \201 ndings are a decreased cardiac outpu t, high systemic vascular resistances and low \201 lling pressures. Hemoglobin can initia lly be maintained in hemorrhage. Cardiogenic shock Cardiogenic shock is due to a failure of the cardiac pump, related either to impaired contractile function or to valvu- lar dysfunction. In addition, it can be glob al, affecting both right and left sides, or predominantly left or right sided. It is import ant to make a precise diagnosis of the cause of car- diogenic shock, as therapy may differ accordingly. The typical clinical presentation is a patient with hypoten- sion, skin vasoco nstriction and dilated jugular veins. Diagnosis: the haemodynamic de \201 nition of cardio genic shock is based on the finding of a decreased and inadequate cardiac index (CI lower t han 2.2l/min/m and low SvO2) in the presence of adequate preload and accom- panied by sig ns of hypoperfusion (decreased blood pres- sure or elevated lactate levels). In this de \201 nition, it is important to evaluate cardiac output, and especially to determine that i t is inadequate for metabolic needs (signs of inadequate tissue perfusion): indeed patients with chronic heart failure may present signs of decreased systo- lic function and dilated ventricules, but cardiac output can be preserved. Evaluation of ventricular preload (pressu re or echo meas- urements) is essential to rule out hypovolaemic shock, but also to differe ntiate right from left side dysfunction Obstructive shock Obstructive shock is due to obstruction of the cardiovas- cular system. T he most common causes are PE and cardiac tamponade. The typical clinical presentation is a patient with hypoten- sion, skin vasoconstriction and dilated jugular veins. Pulsus paradox us is frequent. The typical haemodynamic presentation is a low cardiac output, high SVR, hi gh \201 lling pressures (right in PE, left in aortic dissection, bilateral in tamponade) and pulmonary hypertension in PE. Echocardiography is extremely helpful to diagnose obstruc - tive shock and its cause. Distributive shock Distributive shock is a complex syndrome characterized by profound cardi ovascular derangements, associating a decreased vascular tone, myocardial depression, blood \202 ow redistribution between organs and microcirculatory alterations. In addition, hyp ovolaemia is frequent in its early stages (fluid losses and venous blood pooling in the spl anchnic area). The typical clinical presentation is a patient with hypoten- sion, skin vaso dilation, and acrocyanosis or mottled skin. 448 D DE BACKER The typical haemodynamic picture is a patient with normal to high cardiac output, low blood pressure and low indices of preload who fails to correct his haemodynamic pro \201 le aft er rapid volume infusion. Conference, Paris, France, 27 \200\22328 April 2006 Intensive Care Med 2007; 33: 575 \200 \22390. De Backer D Lactic acidosis Intensive Care Med 2003; 29: 699 \200\223702. Weil MH, Shubin H . Proposed reclassi \201 cation of shock states with special reference to distributive def ects Adv Exp Med Biol 1971; 23: 13 \200\22323. Further reading Antonelli M, Levy M, Andrews PJ, et al. Hemodynamic monitoring in shock and implications for management: International Consensus This page intentionally left blank 450 D DE BACKER Hypovolaemic shock Hemoglobin levels can initially be maintained in haemor- rhage and decrease only after init iation of \202 uid resuscita- tion or when shock is prolonged (volume mobilization from t he extravascular compartment). Hypovolaemic shock is the most common source of shock; it often can easily be reversed, if detected early and pro- vided its cause can be corrected. Pathophysiology of hypovolaemic shock: Hypovolaemic shock is due to a profound reduction in blood volume. Hypovolaemia is associated with an initial decrease in ventricular preload, but the almost immediate increase in endogenous catecholamines limits the decrease in strok e volume (by increasing contractility), while cardiac output is maintained by the compensat ory increase in heart rate. The profound vasoconstriction also helps to redistribute blood volume from the peripheral to the cen- tral compartment, helping to maintain cardiac output and blood pressure. This venous constriction limits the decrease in preload by decreasing the amount of blood stored in large venous capacitance beds (mostly splanchnic veins, but a lso arm and leg veins). It also affects blood \202 ow distribution, so that the limited a mount of blood is redi- rected to the most vital organs. Blood \202 ow to splanchnic orga ns, kidneys and the skin is markedly decreased, while brain and heart circulations are some what preserved. If hypovolaemia persists, these compensatory mechanisms are not suf \201 c ient and cardiac output and blood pressure decrease. These compensatory mechanisms are clea rly vital and ben- e \201 cial in the short term, but unless the hypovolaemia is corrected they will begin to cause deleterious effects. The decrease in kidney perfusion may lead to renal damage and eventually acute tubular necrosis. Myocardial oxygen bal- ance is threate ned by the combination of tachycardia, increased contractility, and increased catecholamine levels in the context of decreased coronary perfusion (due to hypotension). This may lead to myocardial ischaemia and even to MI in patients with coronary lesions. The decrease in s planchnic perfusion may alter the gut defenses and integrity, with the possibility of promo ting translocation of bacteria and bacterial toxins, especially during the reper- fusion ph ase. Therapy Treatment includes control of the source of bleeding and \202 uid replacement (in cluding red blood cell transfusions and coagulation factors). Vasopressor agents may be tra n- siently required. Inotropic agents are usually not required, as contractility is preserv ed (with the exception of patients with underlying cardiac disease or heart trauma). It is rec- ommended that therapy of haemorrhagic shock should not aim at full restoration of bloo d volume and blood pressure while the hemorrhage is not controlled. In bleeding patients, a systolic pressure of 90mm Hg is suf \201 cient to preserve tissue perfusion while limitin g the risk of bleeding. In bleeding patients with brain trauma, a systolic pressure of 120m m Hg should be attained to protect cerebral per- fusion. Once bleeding has been stopped, re suscitation should aim at full restoration of tissue perfusion. Vasopressor agents Vasopressor agents should be used with caution. By improving blood press ure, these agents help to restore organ perfusion, including brain and coronary artery per- fusion. The mechanism of action may mean that there is an additional increase in SVR, whic h may further compromise blood \202 ow in some vascular beds (especially the skin, splanc hnic region and kidneys). These agents should thus always be used at the lowest dose compat ible with ade- quate organ perfusion, essentially buying time for correc- tion of blood vol ume. Vasopressor agents should be weaned once blood volume has been restored, where pos- si ble. If vasopressor agents are still required after correc- tion of hypovolaemia, one shoul d think of an alternative cause of the hypotension (usually distributive shock, either from ischaemia \200\223reperfusion or due to sepsis). Adrenergic agents are still the most comm only used vaso- pressor agents. Dopamine, noradrenaline and adrenaline have variable effect s on A and B receptors. Adrenaline and noradrenaline are the most potent agents. Noradrenal ine has a strong and dose-dependent A effect accompanied by a weak B effect. Adrenaline has similar strong dose- dependent A and B effects. Dopamine has moderate A and B effects and a weak dopaminergic effect. The role of the dopaminergic effect can be questioned as there is no proof of a bene \201 cial effect on splanchnic and renal perfusion, but there are da ta suggesting that the dopaminergic effect may be responsible for the endocrine effects of the drug. Noradrenaline and adrenaline are both very potent pres- sor agents; however, the inotropic, chronotropic and meta- bolic effects of adrenaline are stronger than those of no radrenaline. As patients with hypovolaemic shock are often tachycardic, noradrenaline shoul d be preferred to adrenaline, although the impact on outcome of these dif- ferences have no t been evaluated. Non-adrenergic vasopressor agents, and especially vaso- pressin, may also have a place in the therapy of hemor- rhagic shock. Experimental studies and case reports suggest that vasopressin may be more potent than adrenaline in restoring blood pressure in haemorrhagic shock due to liver laceration. This agent has the advantage of restoring Causes of hypovolaemic shock There are many causes, ranging from bleeding (trauma, digestiv e hemorrhage or other causes of blood losses), to decreased plasma volume (dehydration, mos t commonly due to diarrhea or vomiting) or tissue damage and \202 uid loss such as burns. Children are particularly sensitive to dehydration. Clinical features Presentation; tachycardia, skin vasoconstriction and acro- cyanosis. Hypo tension often occurs, but blood pressure can initially be preserved even with large \202 uid losses, espe- cially in the young. Signs of tissue hypoperfusion are fre- quent (altera tion in mental state, oliguria). Signs of dehydration or anemia may be encountered, but the se may sometimes be missing. Key haemodynamic \201 ndings Hypovolaemic shock is characterized by a decreased car- diac output, high SVR and low \201 lling pressures. In patients on mechanical ventilation, la rge respiratory variations in pulse pressure and stroke volume can be observed. Venous O2 s aturation (mixed venous and central venous) is typi- cally decreased. Lactic acidosis is fr equent. 451 CHAPTER 26.2 Hypovolaemic shock injury is characterized by an activation of in \202 ammation and coagulation, and release of reactive oxygen species. Although related to the severity of tissue hypoperfusion during the ischaemic phase, most of the histological lesions occur during the reperfusion phase. Reperfusion syndrome is characterized by a distributive shock, associated with severe micro vascular and cellular alterations. Despite intense research, no speci \201 c therapy can a ctually be pro- posed. Supportive therapy is similar to the supportive therapy for distribu tive shock. blood pressure but decreasing portal blood \202 ow and por- tal pressure, limiting the ra te of bleeding. In other types of shock, this decrease in splanchnic blood \202 ow is pro bably detrimental and this agent should be used cautiously. There are no adequate studies o f the impact of vasopressin on outcome. Caution is urged when applying sedation or analgesi a to patients with hypovolaemic shock. These agents blunt the release of endogenous catecho lamines, and induce vasodi- lation and myocardial depression. Ketamine, in contrast to othe r morphinic agents, is not associated with these unfa- vourable haemodynamic effects and is thus often consid- ered as the analgesic agent of choice. Positive pressure ventilation re duces ventricular preload, thereby exacerbating the haemodynamic alterations. Initially tid al volume and PEEP should be limited, and these should be progressively increased with caut ion. Further reading Antonelli M, Levy M, Andrews PJ, et al. Hemodynamic monitoring in shock and implications for management: International Consensus Conference, Paris, France, 27 \200 \22328 Apil 2006 Intensive Care Med 2007; 33: 575 \200\22390. Bickell W, Wall M, Pepe PE, et al. Immediate versus delayed \202 uid resuscitation for hy potensive patients with penetrating torso injuries. N Engl J Med 1994; 331: 1105 \200\2239. The reperfusion phase Reperfusion injury is common after recovery from severe hypovolaemic/ haemorrhagic shock. Ischaemia \200\223reperfusion Meybohm P, Cavus E, Bein B, et al. Small volume resuscitation: a randomized controlled tria l with either norepinephrine or vaso- pressin during severe hemorrhage. J Trauma 2007; 62: 640 \200\2236. 452 G VOGA Cardiogenic shock De \201 nition, incidence, causes Cardiogenic shock is de \201 ned as a state of inadequa te tissue perfusion due to cardiac failure. Most commonly caused by pump failure in patient s with AMI or mechanical complica- tions of AMI (acute MR, ventricular septal defect, cardi ac tamponade due to LV rupture, or pericardial effusion), or myocarditis, myocardial contus ion, septic myocardial depression, LV out \202 ow obstruction, stress-induced cardio- myop athy, intoxication with cardiodepressant substances (B-blockers, calcium channel antagonist s, etc.). It occurs in 6 \200\2239% of patients with AMI. Shock is present on hospital admi ssion in <1% of patients with AMI. In others, shock usually develops during the \201 rst days of hospitalization, most commonly in older women with previous CAD, con- comitant peri pheral arterial diseases and cerebrovascular disease, diabetes and hypotension, tachycardia and Killip class III or IV on admission . The differential diagnosis of cardiogenic shock includes AMI or ischaemia associated with s evere aortic stenosis. Hemorrhage during thrombolytic treatment can result in haemorrhagic shock, and septic shock can develop in patients with multiple intravascular lines. Recognit ion is important as these diagnoses need a different management approach Diagnosis The diagnosis and etiology should be con \201 rmed as soon as possible. Routine investigations include ECG, CXR and laboratory tests, which should include blood gas analys is, lactate and troponin measurement. Early TTE is mandatory for aetiological diagnosis and initial haemodynamic assess- ment in every patients with suspected cardiogenic shock. It e nables rapid and reliable assessment of morphology, glo- bal and regional systolic function of the left and right ven- tricle, LV diastolic function, valvular morphology and function , and recognition of cardiac tamponade, PE and dis- section of the proximal aorta. It is es pecially helpful for early diagnosis of mechanical complications of AMI. In the case of ina dequate visualization or non-conclusive \201 ndings, TOE can be performed. Low LVEF and s everity of MR on echo examination are important predictors for poor out- come. Invasive hae modynamic measurements using an intra-arte- rial catheter and Swan Ganz pulmonary catheter allow haemodynamic diagnosis and continuous monitoring of haemodynamic variables (arterial pressure, CVP, PAP, PAOP, SvO2, cardiac output, RV end-diastolic volume and EF), evaluation of the therapeutic effects and precise titration of the drugs. Invasive arterial pressure monitoring is man- datory in patients treated with vasopressors or vasodila- tors and patie nts with severe hypotension. The routine and early use of echocardiography signi \201 cant ly decreases the use of a pulmonary artery catheter; it is still useful and necessary in pa tients with unstable haemodynamics, those who do not respond to the treatment and those wit h pro- gressive pulmonary congestion or hypotension. In some centers, acute coronary angiog raphy can be per- formed in cardiogenic shock due to AMI, allowing con \201 r- mation of t he diagnosis and immediate interventional treatment. Symptoms and signs Often associated with anterior MI. Beside typical retroster- nal pain, p atients have symptoms and signs of severe tis- sue/organ hypoperfusion (cyanosis, cold and clammy skin, slow capillary re \201 lling, mental changes, obtundation, oligu- ria) and pu lmonary congestion (dyspnoea, tachypnoea, orthopnoea). Signs of tissue hypoperfusion are pr esent in 92%, signs of pulmonary congestion in 70% and both in 68% of patients. Haemodynami c characteristics include tachy- cardia, hypotension, low cardiac output, elevated cardiac \201 lling pressures, increased SVR and low mixed venous oxy- gen saturation (SvO2). Hypo tension, which is de \201 ned as an SBP <90mm Hg or decrease of MAP of >30mm Hg from the p atient \200\231s normal level, is common in cardiogenic shock. It is the result of decrease d stroke volume, which cannot be compensated by arterial vasoconstriction. The combi- natio n of low cardiac output and systemic vasoconstriction results in severe tissue hypoperfusio n and decreased coro- nary artery blood \202 ow, which further worsen the cardiac perform ance. In some patients with cardiogenic shock, sys- temic arterial vasodilatation is presen t, most probably because of the systemic inflammatory response with cytokine release and el evated NO level, which provokes further systemic and coronary hypoperfusion and directly de creases myocardial contractility. Predominant RV failure complicates inferior MI with exten - sion to the RV. It is characterized by hypotension and ele- vated RV \201 lling pressur e without pulmonary congestion. It is easily detected and con \201 rmed by echocardiograph y, which shows an enlarged and hypokinetic RV. Acute MR can be the consequence of ischaemic papillary muscle dysfunction or rupture of papillary muscle or chor- dae tendineae. Charac terized by sudden and refractory pulmonary oedema, shock and new apical systolic murmur, it is associated with poor prognosis. A new systolic mur- mur, together with acute left to ri ght shunt, is characteristic for ventricular septum rupture. Both complications of AMI are usually recognized and con \201 rmed by TTE or TOE. Cardiogenic shock is seen in stress-in duced cardiomyopa- thy (tako-tsubo syndrome or transient apical ballooning), which occurs m ost commonly in post-menopausal women with normal coronary arteries after severe physical o r emotional stress. Because of transient LV dysfunction and rapid recovery, prognosis is ex cellent. Treatment Cardiogenic shock necessitates ICU admission and inten- sive care monitoring and treatment: optimal oxygenation, correction of electrolyte and acid \200\223base disturbance s, tight glucose control, stress ulcus prophylaxis, early oral feeding, upright position in ventilated patients and sedation with analgesia. After obtaining the aetiological and haem ody- namic diagnosis, patient should be haemodynamically stabi- lized by using \202 uid c hallenge in those without pulmonary oedema and vasopressors in those with hypotension unre- sponsive to \202 uids. Preload should be assessed repetitively and optimized by giving b oluses of crystalloid or colloid infusion. The changes of haemodynamic variables (heart rat e, arterial pressure, CVP, PAOP, cardiac output, ScO2) and oxygenation (SaO2) should be mon itored closely to prevent pulmonary oedema and hypoxaemia, and to evaluate the response to the treatment. Inadequate cardiac \201 lling can be also pro- voked by intensive diuretic and vasodilator treatment and 453 CHAPTER 26.3 Cardiogenic shock oxygenation, left atrial to femoral arterial ventricular assist device and impeller pump in side the catheter) can be suc- cessfully used in specialized centers. Mechanical ventilatio n when necessary should be started early to reduce increased work of breathing and allow ve n- tilation with high FiO2 and PEEP. Positive inspiratory pres- sure often has favorable ha emodynamic effects in patients with heart failure by decreasing venous return, and enhances LV ejection by decreasing LV afterload and hence reducing congestion. Weaning from a venti lator can be dif- \201 cult in patients with LV failure and should be planned carefully. Close monitoring is mandatory. In patients with AMI, antiaggregation with aspirin and clopi - dogrel is usually started together with heparin which pre- vents DVT and can maintain cor onary artery patency. Early thrombolytic therapy improves the outcome and reduces the incid ence of cardiogenic shock in patients with STEMI and should be started as soon as possible. Alteplase, tenecteplase and reteplase are preferred, since they are more effective than st reptokinase which is considerably less expensive. The contraindications for thrombolytic th erapy should be checked before the treatment, and patients must be regularly examined for p ossible bleeding. However, thrombolysis alone is not effective in patients with cardiogenic shock unless it is used together with an IABP. If unsuccessful, thrombolysis and persisten t shock patients should be referred for rescue PCI or CABG. PCI signi \201 cantly reduces early and late mortality from car- diogenic shock and is preferred to thrombolysis in patie nts with AMI complicated by cardiogenic shock. PCI should be performed as soon as possible in patients with cardiogenic shock, and an IABP can be inserted before or immediately after PCI. However, the outcome in patients treated by IABP is not signi \201 cantly better and is related to the skill and frequency of using the device. Experimentally, l-NMMA (tilargi nine acetate), an inhibitor of nitric NOS was used to reverse the severe cardiogenic shock with vasodilation due to excessive cytokine and NO production. The results were promising i n the small number of patients, but unfortunately they have not been con \201 rmed in a ne w larger trial. should be considered, recognized and corrected in every phase of acute heart failure and ca rdiogenic shock. Preload assessment is most accurately performed by measuring LV volume/are a by echocardiography. Nevertheless, \201 lling pressures (CVP and/or PAOP) are commonly used, despite the fact that they are poor measures of preload. The trends and responses to the treatment are much more important that the static measurements. Vasoactive and inotropi c drugs remain the mainstay of \201 rst-line treatment despite the fact that they are of very limited success. Commonly used vasopressor and inotropic drugs are listed in Table 26. 3.1. In general, vasopressors increase afterload. Dobutamine tends to dilate but increases myocardial oxygen consumption. Both can nega- tively affect cardiac performance, especially in patients with ACS. Selection depends on degree of hypotension, impair- ment of contract ility and presence or absence of pulmo- nary congestion. The absolute prerequisite for vaso pressor and inotropic treatment is adequate cardiac preload. In hypotensive patients, dopam ine is still often used as a \201 rst agent, but its effect is limited by increase of hea rt rate and elevation of pulmonary pressure. In patients with profound hypotension, norepin ephrine is the most ef \201 cient vaso- pressor used. Dobutamine, which is the \201 rst- line inotropic agent, can be combined with nitroglycerin or sodium nitro- prusside in patie nts with pulmonary congestion. Levosimendan, a new potent inotropic and vasodilator drug, w hich does not increase myocardial oxygen con- sumption, has been successfully used in cardi ogenic shock. Frequent titration of various drugs to modify haemody- namic variables may be necessary, and cardiac output and its adequacy should be measured. Since the main indicati on for inotropic support is inadequate cardiac output, the measurement of adequacy is of ut most importance. The best way to monitor the adequacy is continuous measure- ment of SvO2, which re \202 ects the oxygen extraction rate. Monitoring the trend of cardiac output is h elpful for evalu- ation of the treatment effect. Mechanical support with an intra-aortic ba lloon pump (IABP) should be used in intractable shock. In profound shock or severe left hea rt failure, an IABP should be inserted even before using the drugs for haemodynamic stabili zation. An IABP can rapidly stabilize the cardiogenic shock by improving coronary and syste mic blood \202 ow and reducing systolic afterload. However, without previous revasculariz ation in patients with AMI (PCI, CABG or thrombolysis), the effect of an IABP is only tempo rary. Beside IABPs, other mechanical devices (LV assist device, percutaneous cardiopulmonar y bypass with extracorporeal Prognosis Mortality rate for cardiogenic shock was 80 \200\22390% in the 1970s and 1980s, b ut shows a continuous decrease with the use of aggressive reperfusion strategies and of the IABP. The mortality is now 55 \200\22365%, with the exception of unchanged high mortality in patients with ventricular Table 26.3.1 Vasopressor and inotropic drugs Drug Dose Heart rate Contractility Vasoconstriction Vasodilation 1 \200\2234 g/kg/min Dopexamine ++ + 0 + 1 \200\2235 g/kg/min Dopamine ++ ++/+++ ++/+++ 0 0.1 \200\2230.5 g/kg/min Norepinephrine + ++ ++++ 0 0.1 \200\2230.5 g/kg/min Epinephrine ++++ ++++ ++++ ++ at low dose only 2 \200\22320 g/kg/min Dobutamine ++ ++++ 0 ++ Bolus 50 g/kg over 10 minutes 0.375 \200\2230.75mcg/kg/min Milrinone + +++ 0 ++ Levosimendan Bolus 6 \200\22312mcg/kg 0.05 \200\2230.2 g/kg/min + ++++ 0 +++ 454 G VOGA septum rupture. Mortality is similar in patients with STEMI and NSTEMI. Predictors of morta lity are increasing age, prior MI, severe clinical manifestation on admission, oligu- ria, low EF, and MR by echocardiography, three-vessel or left main coronary artery disease and u nsuccessful revas- cularization. Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) tri al. Circulation 1997; 96: 122 \200\2237. Cotter G, Kaluski E, Milo O, et al. LINCS: l-NAME (a NO synthase inhibitor) in the treatment of refractory cardiogenic shock: a pro- spective randomized study. Eur Heart J 2003; 24: 1287 \200\22395. French JK, Feldman HA, Assmann SF, et al. In \202 uence of thrombolytic therapy, with or w ithout intra-aortic balloon counterpulsation, on 12-month survival in the SHOCK trial. Am H eart J 2003; 146: 804 \200\22310. Further reading Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the managem ent of patients with ST-elevation myocardial inf- arction. J Am Coll Cardiol 2004; 44: 671 \200\223719. Hochman JS Cardiogenic shock complicating acute myocardial inf- arction: expanding the para digm. Circulation 2003; 107: 2998 \200\223 3002. Babaev, A, Frederick, PD, Pasta, DJ, et al Trends in management and outcomes of patients wi th acute myocardial infarction compli- cated by cardiogenic shock. JAMA 2005; 294: 448 \200 \22354. Picard MH, Davidoff R, Sleeper LA, et al Echocardiographic predic- tors of survival and r esponse to early revascularization in cardio- genic shock. Circulation 2003; 107: 279 \200 \22384. Barron HV, Every NR, Parsons LS, et al. The use of intra-aortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction Am Heart J 2001; 141: 933 \200\2239. The TRIUMPH Investigators. Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: The TRIUMPH randomized controlled trial. JAMA 2007; 297: 1657 \200\22366. Berger PB, Holmes DR, Stebbins AL, et al. Impact of an aggressive invasive catheterization and revascularization strategy on mortal- ity in patients with cardiogenic shock in the Glo bal Utilization of This page intentionally left blank 456 K SIM & N WEBSTER Anaphylactic shock to the critical illness. The intubated patient provides a diag- nostic challenge as early f eatures of anaphylaxis are likely to go unnoticed. Thus a high level of clinical suspicion must be maintained. It must be remembered that anaphylactic reactions, although typically r apid in onset, may occasion- ally develop over a number of hours. Anaphylactic shock is a life-threatening multi-system disor- der, caused typically by an Ig E-mediated type 1 hypersensi- tivity reaction. The incidence of anaphylactic reactions is d if \201 cult to quan- tify (no consensus on de \201 nition); however, a recent sympo- siu m suggested that any \200\230allergic reaction that is rapid in onset and may cause death \200\231 is, by de \201 nition, anaphylactic. It is estimated that 1 in 3000 in-patients ( in the USA) suffer an anaphylactic reaction \200\2241% of all anaphylactic reactions are fa tal, so prompt recognition and treatment of the con- dition is essential. Critical care cli nicians are likely to encounter patients suffering anaphylaxis from drugs administered in t he critical care setting or in patients referred to ITU following a reaction. Cutaneous \200 Flushing \200 Angioedema \200 Urticaria Respiratory \200 Cough \200 Hoarseness \200 Stridor \200 Bronchospasm \200 If ven tilated a sudden rise in airway pressures may be noted Pathophysiology Allergy to a substance occurs via a number of steps. 1 On \201 rst exposu re to an allergen, IgE antibodies speci \201 c Cardiovascular \200 Palpitations \200 Tachycardia \200 Arrhythmias \200 Hypotension \200 Collapse to that allergen are produced by B cells. 2 These antibodies bind to mast cells and basophils and cause them to be \200\230sensitized \200\231. 3 Further exposure to the allergen causes cross-linking of bound IgE, resulting in degranulation. Mast cell degranulation leads to the release of a number of vasoactive mediators including histamine, prostaglandins, tryptase, platelet-activating factor and leukotrienes. The combi ned effect of these mediators is to produce vasodila- tation, increased vascular permeabili ty, oedema and, in cases of anaphylaxis, smooth muscle spasm in the respira- tory and GI tr acts. Chemotactic mediators are also released, attracting eosinophils to the site of in \202 ammation. Anaphylactoid-type reactions cause mast cell degranula- tion with release of mediators, as above, but do not involve IgE cross-linkage and so do not require prior expo sure to the causative agent. Clinical features and management are identical to those of ana phylactic reactions. Differential diagnosis Other conditions which should be considered when faced with the above symptoms and signs in clude: \200 \200 \200 \200 \200 Acute asthma attack/bronchospasm Tension pneumothorax Myocardial infarction Airway obstruct ion Acute hypovolaemia Table 26.4.1 Typical precipitants of anaphylaxis on ICU Clinical approach History \200 Antibiotics \200\224most commonly penicillins; cross-sensitivity of 10% with cephalosporins must be remembered