Ebook Cardiac arrest - The science and practice of resuscitation medicine (2nd edition): Part 2

Part V Postresuscitation disease and its care 47 Postresuscitation syndrome Erga L. Cerchiari Department of Anaesthesia and Critical Care, Ospedale Maggiore, and Area of Anaesthesia and Critical Care, Surgical Department, Provincial Health Care Structure, Bologna, Italy The postresuscitation syndrome (PRS) has been defined as a condition of an organism resuscitated following prolonged cardiac arrest, caused by a combination of whole body ischemia and reperfusion, and characterized by multiple organ dysfunction, including neurologic impairment.1 Background Following resuscitation from cardiac arrest, patients either recover consciousness or remain unconscious, depending on the duration of cardiac arrest and the effectiveness of any CPR, but also on prearrest conditions such as age and comorbidities.2 Shorteningno-flowtimesbytimelyinterventionsthatcan maintain some perfusion and promote the restoration of spontaneouscirculation(e.g.,bystanderCPR,earlydefibril-lation, and other means) improves the possibility of a suc-cessfuloutcomewiththepatientrecoveringconsciousness.3 The wider availability of resuscitation techniques to reverse clinical death, however, has led to increasingly fre-quent observations of a pathological condition occurring in patients who remain unconscious, involving multiple organ injury or failure following reperfusion after pro- longed cardiac arrest. The concept of postresuscitation disease as a unique and new nosological entity was introduced by Negovsky in 1972;4,5 the most interesting aspect of this innov- ative concept was the recognition that the etiology dependedonacombinationofseverecirculatoryhypoxia with the unintended sequelae of measures used for resuscitation. On the basis of the wide variety of ischemic/hypoxic mechanisms that can trigger its development, the disease was redefined by Safar as a syndrome in which patho-genetic processes triggered by cardiac arrest were exacer-bated by reperfusion, causing damage to the brain and other organs, the complex interactions of which combine to determine overall outcome (see early experimental find-ings summary).6,7 The evidence of features common to the postresus-citation syndrome and multiple organ dysfunction syn-drome led to the hypothesis that a systemic inflammatory response of the entire organism was triggered by ischemia and reperfusion, adding to the damage directly induced by ischemia during cardiac arrest.8 Two landmark studies, showing that mild therapeutic hypothermia started after reperfusion can improve recov-ery after cardiac arrest, confirm that outcome is deter-mined not only by events occurring during arrest and CPR but also by pathogenetic processes continuing after reperfusion.9,10 Recent reports confirm the occurrence of a “sepsis-like syndrome” after resuscitation from cardiac arrest,11,12 although the mechanistic relationship to the direct damage induced by ischemia during cardiac arrest has yet to be clarified. Cardiac Arrest:The Science and Practice of Resuscitation Medicine. 2nd edn., ed. Norman Paradis, Henry Halperin, Karl Kern, Volker Wenzel, Douglas Chamberlain. Published by Cambridge University Press. © Cambridge University Press, 2007. 817 818 Erga L. Cerchiari Early Experimental Findings Negovsky4,5 andhisgroupofRussianinvestigatorspioneeredtheconceptofpostresuscitationdiseaseasauniquenoso-logical entity, caused by the combination of severe hypoxia and resuscitation, on the basis of hundreds of experimental observations that fall into three groups: 1. Phasic Pattern of Postresuscitation Recovery Independent of the type of insult, alterations in cerebral and extracerebral organs occur starting with reperfusion and developing over time. From insult to 6 to 9 hours postinsult: rapid changes in cerebral and systemic hemodynamics, metabolism, and rheol-ogy (clotting disturbances, increased viscosity), increase levels of biologically active substances and prostaglandin deriv-atives; alterations of the immune system (increased bactericidal activity, depressed reticuloendothelial system, and hyperreactivity of B- and T-lymphocytes), and toxic factors in the blood (peptide fraction 800 to 2000 Daltons and endo-toxin secondary to gram-negative bacteremia). From 10 to 24 hours postinsult:normalization of cardiovascular variables and progression of metabolic derangements ensue. During this time, 50% of deaths occur as a result of recurrent cardiac arrest. From 1 to 3 days postinsult: stable cardiovascular variables and improvement in cerebral function associated with increased intestinal permeability leading to bacteremia. The stabilization phase (more than 3 days postinsult): characterized by the prevalence of localized or generalized infection that represents the major cause of delayed deaths. The degree of cerebral and extracerebral organ derange-ments is reported to be more severe and prolonged the longer the duration of the hypoxic–ischemic insult. 2. Interactions between Cerebral and Extracerebral Postischemic Damage on Outcome The severity of systemic and hemodynamic derangements after 20 minutes of isolated brain ischemia is comparable to that recorded after only 12–15 minutes of total circulatory arrest with ventricular fibrillation, suggesting that cerebral postischemic damage plays a role in development of extracerebral dysfunction, probably by inducing changes in neu-rohumoral regulation. Cerebral function recovers better after bloodless global brain ischemia than after the same duration of circulatory arrest from ventricular fibrillation, leading to the conclusion that extracerebral factors account for about half of the pathological findings in the brain induced by cardiac arrest. 3. Benefical Effect of Trials with Detoxification Techniques A series of trials aimed at removing toxins and normalizing homeostasis by various detoxification techniques showed that all the techniques can improve neurological recovery and survival compared with concurrent controls; cross-cir-culation was the most effective, in which circulation in the body of the resuscitated dog was maintained for 30 minutes post-ROSC by the heart of a healthy donor dog, aided by an extracorporeal circulation system. Safar and his group in Pittsburgh, in parallel with – but subsequent to – the Russian experimental work, confirmed that extracerebral organ dysfunction may hamper cerebral recovery following resuscitation from cardiac arrest, based on the observations that (a) cerebral function after isolated global brain ischemia recovers better than after compara-ble durations of total body ischemia13,14 and (b) the use of cardiopulmonary bypass for resuscitation and for short-term postresuscitation assistance improves myocardial performance after weaning, and significantly increases neurological outcome and survival.15 Extracerebral organ dysfunction following resuscitation from cardiac arrest of increasing dura-tions was studied in animal experimental models:1,6,7,14–19 · cardiac output and arterial oxygen transport, after a transient increase, showed a prolonged and profound decrease associated with increased peripheral resistance; this starts sooner and is more severe and prolonged after longer durations of VF, resolving by 12 to 24 hours postresuscitation · pulmonary gas exchange, with assisted ventilation for 6 to 24 hours postresuscitation, is well maintained even after extubation (normoxia, normocarbia, and rapid pH normalization) · coagulation disturbances with hypocoagulability start during resuscitation, with prolonged clotting times and decreased platelets and fibrinogen, and normalize at 24 hours after resuscitation; elevated fibrin-degradation prod-ucts and decreased platelet counts were observed to 72 hours postresuscitation. Postresuscitation syndrome 819 · erythrocyte count decreases significantly · renal function (blood urea nitrogen, serum creatinine, osmolarity, sodium, potassium, and calcium) remain normal after a transient reduction in urine output with positive fluid balance, normalizing at 3 to 6 hours · hepatic function is altered transiently; plasma ammonia and branched chain and aromatic amino acids increase, with higher levels in the animals with poor outcome, suggesting an alteration of liver-detoxifying function · bacteremia is a constant feature after cardiac arrest, with transient leukocytosis but without hyperthermia (90% were constituents of the intestinal flora, suggesting postischemic bacterial translocation). In summary, following resuscitation from cardiac arrest, multiorgan dysfunction occurs, but the abnormalities have different time patterns (Fig. 47.1). 100 80 60 40 Cardiovascular 20 Clotting/Fibrinolysis 0 Neurologic Neurologic Clotting/Fibrinolysis Cardiovascular Fig. 47.1. Time pattern of organ dysfunction after resuscitation from cardiac arrest from the early experimental work.1,4–7 Incidence and prevalence The incidence of out-of-hospital cardiac arrest is estimated to be 49.5–66 per 100 000 cases per year:2 in these, return of spontaneous circulation can be achieved in 17% to 33%, depending on the efficiency of the emergency response system.20 The incidence of in-hospital cardiac arrest has been esti-mated as 1.4/100 admissions/year:21 in these cases, restora-tion of spontaneous circulation occurs in 40%–44%.22 Of the patients resuscitated from cardiac arrest, a small proportion (variable as a function of timeliness and effectiveness of response) achieve early recovery, with restoration of spontaneous respiration and consciousness. Identification and treatment of the cause of arrest is the mainoronlytherapeuticchallengeforthisgroupofsubjects. But most survivors of cardiac arrest (80%) are comatose postresuscitation, and are admitted to the ICU where they represent the population of patients with postresuscita- tion syndrome (PRS), amounting to about 15%–20% of all cardiac arrest victims (Fig. 47.2). Among the PRS patients, mortality has been reported to be very high, reaching 80% by 6 months postresuscita-tion:23–25 approximately one-third of the deaths are due to cardiac causes (early deaths usually,24 hours), one-third to malfunction of extracerebral organs, and one-third to neurologic causes (late deaths). The prevalence of the postresuscitation syndrome can only be inferred, because of the bias of data resulting from decisions to limit treatment, including instructions for “do not attempt resuscitation,” in cases of recurrent cardiac arrest.22–26 Etiology Following resuscitation from cardiac arrest of less than 5 minutes, recovery is rapid and complete. After prolonged arrest, ROSC is impossible or only transient. ... - tailieumienphi.vn