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Early Prognosis in Coma After Cardiac Arrest: a Prospective Clinical, Electrophysiological, and Biochemical Study of 60 Patients

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Early Prognosis in Coma After Cardiac Arrest: a Prospective Clinical, Electrophysiological, and Biochemical Study of 60 Patients 61060ournal ofNeurology, Neurosurgery, and Psychiatry 1996;61:610-615 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.6.610 on 1 December 1996. Downloaded from Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and biochemical study of 60 patients C Bassetti, Fulvio Bomio, Johannes Mathis, Christian W Hess Abstract estimate, neuronal damage must be assessed Background-The univariate study of indirectly by exploring cerebral functions and clinical, electrophysiological, or bio- evaluating their pattern of recovery over time. chemical variables has been shown to In general, the longer the delay in recovery of predict the outcome in postanoxic coma function the worse the prognosis. Due to the in about 50% of patients for each type of greater vulnerability of the cerebral cortex to variable. Previous studies did not, how- hypoxia than the brainstem, recovery usually ever, consider the prognostic accuracy of occurs in a caudorostral sequence,5 and the a multivariate approach. maximal recovery time still compatible with a Methods-Sixty patients in coma for good outcome depends on the neurological more than six hours after cardiac arrest function being considered. Several studies were prospectively examined by means of have shown that the duration and depth of repeated clinical examinations (including coma are good predictors of outcome.3'5 6 7 The Glasgow coma score (GCS)), EEG, and absence of brainstem reflexes for more than six medianus nerve somatosensory evoked to 24 hours after cardiopulmonary resuscita- potentials (SEPs). In 16 patients, the tion,3589 absent motor responses to pain for early concentrations of serum neuron more than one or two days,371011 the persis- specific enolase and ionised calcium were tence of a Glasgow coma score (GCS) < 5 for also measured. more than two or three days,67 and of a GCS Results-Within the first year after car- < 8 for more than one week36 all herald a poor diac arrest, 20% of patients made a good outcome. However, clinical prognostication neurological recovery; 80% remained in a within the first few days after cardiopulmonary vegetative state or died. Clinical exami- resuscitation is afflicted with incontestable nation correctly predicted outcome in limitations. Firstly, there is a risk of false pes- 58% of patients, SEP in 59%, and EEG in simistic predictions,'2 which may be as high as 41%. The combination of clinical exami- 5% to 1 0%.13 14 Secondly, brainstem functions nation, SEP, and EEG raised the percent- normalise in most patients within a few hours age of correct predictions to 82%, without and accurate prediction of outcome in these false pessimistic predictions. Concen- patients is not possible within the first two trations of serum neuron specific enolase days after cardiopulmonary resuscitation, as and ionised calcium were of no additional even a GCS of 3 is compatible with a good http://jnnp.bmj.com/ prognostic help. Multivariate regression outcome.3 7 15 16 Thirdly, the accuracy of clini- analysis identified the association of GCS cal parameters is limited in intubated patients < 8 at 48 hours with abnormal or absent who often need muscle relaxation and seda- early cortical SEPs as highly predictive of tion. For these reasons, an intense search for a bad outcome (risk = 97%, 95% confi- electrophysiological and biochemical criteria dence interval = 86-99%). for prognosis in postanoxic coma has been Conclusion-The combination of GCS at undertaken. The absence of continuous EEG 48 hours, SEP, and if these are non- activity for more than eight hours after car- on September 24, 2021 by guest. Protected copyright. conclusive, EEG, permits a more reliable diopulmonary resuscitation,5 the presence of a prediction of outcome in postanoxic coma periodic or "burst suppression" EEG,'7-19 and than clinical examination alone. the absence of early cortical SEPs'6 20-22 in the first two to three days have been shown to be Department of (J Neurol Neurosurg Psychiatry 1996;61:610-615) reliable predictors of a bad outcome. More Neurology recently, biochemical parameters such as C Bassetti J Mathis serum glucose at admission,2 serum ionised CW Hess Keywords: cardiac arrest; postanoxic coma; Glasgow calcium,23 CSF creatine kinase,22 24 CSF lac- coma scale; electroencephalography; somatosensory tate,25 and serum neuron specific Department of evoked potentials enolase,26 Medicine, University have been suggested as potential "markers" of Hospital (Inselspital) diffuse cerebral ischaemia. Their prognostic Bern, Switzerland F Bomio Up to 44% of patients with cardiac arrest can accuracy, however, remains to be confirmed. Correspondence to: be resuscitated successfully.' Most remain Despite considerable information about the Dr C Bassetti, Department comatose initially and only 10%-20% make a prognostic accuracy of single parameters of Neurology, University '3 Hospital (Inselspital) 3010 good recovery. Prediction of individual out- alone, the value of a multivariate approach has Bern, Switzerland. come is a difficult task with important med- not yet been determined. Clearly, the com- Received 29 January 1996 ical, ethical, and socioeconomic implications.4 bined analysis of, for example, clinical exami- and in revised form 13 August 1996 As the duration and severity of cerebral nation, EEG, and SEP has the potential Accepted 19 August 1996 ischaemia are usually unknown or difficult to advantage of giving a more complete func- Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and biochemical study of 60 patients 611 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.6.610 on 1 December 1996. Downloaded from tional profile of a patient. To assess whether a Table 1 Grading ofEEG and medianus somatosensory multivariate approach provides a better pre- evoked potentials (SEPs) diction of outcome within the first three days EEG Grade I Dominant normally distributed a activity, reactive after cardiopulmonary resuscitation, we pro- Grade II Dominant 0-6 activity, reactive spectively studied a consecutive series of Grade III 6-0 activity without a activity Reactive or non-reactive patients in postanoxic coma with a standard Grade IV* "a or 0 coma", non-reactive examination protocol which included repeated Grade IV Burst suppression activty Low voltage 6 activity, non-reactive clinical examinations, EEG, and SEP, serum Periodic general phenomena with isoelectric ionised calcium, and serum neuron specific intervals Grade V Very low voltage EEG enolase. Isoelelectric EEG SEP Grade I Normal N20/P25 response bilaterally (normal amplitude + normal central conduction Patients and methods time) We studied a series of 60 consecutive patients Grade II Abnormal N20/P25 response unilaterally or bilaterally (amplitude reduction > 50% or after cardiac arrest and cardiopulmonary CCT > 7-2 ms, or both) resuscitation who remained comatose, as Grade III Absent N20/P25 bilaterally defined elsewhere,3 for more than six hours. The average age was 62 years, ranging from 19 to 86 years, and 49 were men. Patients with craniocerebral trauma, pre-existing intra- Biochemical studies were carried out in 16 cranial lesions, or drug intoxication were patients. Serum neuron specific enolase con- excluded. All patients were initially intubated, centrations were determined in heparinised most received slight hyperventilation, intra- blood 12 and 24 hours after cardiopulmonary venous nutrition, and slight sedation with resuscitation. Concentrations in serum were midazolam or morphine. Intensive care treat- measured by a commercially available ment was guaranteed in all patients for at least radioimmunoassay (Pharmacia-PDF-Sweden). the first three days after cardiopulmonary The concentration of serum neuron specific resuscitation. enolase measured in healthy subjects in our Repeated clinical examination was per- laboratory is < 20 m mol/l. Ionised calcium, formed in each patient at regular intervals total calcium concentrations, and pH were between six to 12 hours, at 24 hours, at 48 determined in an arterial sample of hours, and at one week after cardiopulmonary heparinised blood four and 12 hours after car- resuscitation. All clinical assessments were diopulmonary resuscitation. Measurements performed by two of us (CB, FB). Glasgow were performed with a calcium selective elec- coma score (best 15, worst 3), corneal, pupil- trode and corrected for a pH of 7-4. The nor- lar, and oculocephalic brainstem reflexes, the mal range of ionised calcium concentrations in presence of spontaneous flexor ("decortica- healthy subjects in our laboratory is tion") or extensor ("decerebration") postur- 1 20-1 30 mmol/l, and for total calcium it is ing, and myoclonic or epileptic phenomena 2-10-2-50 mmol/l. were noted. Outcome was defined as the best cerebral Electrophysiological studies were carried performance achieved at any follow up time out within the first three days after cardiopul- and classified by analogy with the GOS into monary resuscitation in all but four patients; two groups: (1) good outcome: awakening http://jnnp.bmj.com/ EEG and SEP were always recorded 12 hours with reappearance of signs of cognition or more after cardiopulmonary resuscitation, (Glasgow outcome scale (GOS) 3-5); (2) bad as even an isoelectric EEG before this interval (poor) outcome: persistent vegetative state or does not exclude full recovery.27 In 48 patients death (GOS 1-2). Outcome was evaluated at both EEG and SEPs were recorded within 24 one, two,
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