Albert Hijdra

Systematic review of early prediction of poor outcome in anoxic- ischaemic coma

BACKGROUND Studies to assess the prognostic value of early neurological and neurophysiological findings in patients with anoxic-ischaemic coma have not led to precise, generally accepted, prognostic rules. We did a systematic review of the relevant literature to assess whether such rules could be derived from the combined results of these studies. METHODS From Medline and Embase databases we selected studies concerning patients older than 10 years with anoxic-ischaemic coma in which findings from early neurological examination, electroencephalogram (EEG), or somatosensory evoked potentials (SSEP) were related to poor outcome--defined as death or survival in a vegetative state. We selected variables with a specificity of 100% for poor outcome in all studies, and expressed the overall prognostic accuracy of these variables as pooled positive-likelihood ratios and as 95% CIs of the pooled false-positive test rates. FINDINGS In 33 studies, 14 prognostic variables were studied, three of which had a specificity of 100%: absence of pupillary light reflexes on day 3 (pooled positive-likelihood ratio 10.5 [95% CI 2.1-52.4]; 95% CI pooled false-positive test rate 0-11.9%); absent motor response to pain on day 3 (16.8 [3.4-84.1]; 0-6.7%); and bilateral absence of early cortical SSEP within the first week (12.0 [5.3-27.6]; 0-2.0%). EEG recordings with an isoelectric or burst-suppression pattern had a specificity of 100% in five of six relevant studies (pooled positive-likelihood ratio 9.0 [2.5-33.1]; 95%CI pooled false-positive test rate 0.2-5.9%). These characteristics were present in 19%, 31%, 33%, and 33% of pooled patient populations, respectively. For the 11 SSEP studies, results did not significantly differ between studies in which the treating physicians were or were not masked from the test result, prospective and retrospective studies, studies with short and long follow-up periods, and studies with high or low overall poor outcome. INTERPRETATION SSEP has the smallest CI of its pooled positive-likelihood ratio and its pooled false-positive test rate. Because evoked potentials are also the least susceptible to metabolic changes and drugs, recording of SSEP is the most useful method to predict poor outcome.

Prediction of poor outcome within the first 3 days of postanoxic coma

Objective: To determine the optimal timing of somatosensory evoked potential (SSEP) recordings and the additional value of clinical and biochemical variables for the prediction of poor outcome in patients who remain comatose after cardiopulmonary resuscitation (CPR). Methods: A prospective cohort study was conducted in 32 intensive care units including adult patients still unconscious 24 hours after CPR. Clinical, neurophysiologic, and biochemical variables were recorded 24, 48, and 72 hours after CPR and related to death or persisting unconsciousness after 1 month. Results: Of 407 included patients, 356 (87%) had a poor outcome. In 301 of 305 patients unconscious at 72 hours, at least one SSEP was recorded, and in 136 (45%), at least one recording showed bilateral absence of N20. All these patients had a poor outcome (95% CI of false positive rate 0 to 3%), irrespective of the timing of SSEP. In the same 305 patients, neuron-specific enolase (NSE) was determined at least once in 231, and all 138 (60%) with a value >33 μg/L at any time had a poor outcome (95% CI of false positive rate 0 to 3%). The test results of SSEP and NSE overlapped only partially. The performance of all clinical tests was inferior to SSEP and NSE testing, with lower prevalences of abnormal test results and wider 95% CI of false positive rates. Conclusion: Poor outcome in postanoxic coma can be reliably predicted with somatosensory evoked potentials and neuron-specific enolase as early as 24 hours after cardiopulmonary resuscitation in a substantial number of patients.

Perimesencephalic hemorrhage A nonaneurysmal and benign form of subarachnoid hemorrhage

We studied 28 patients with subarachnoid hemorrhage and normal angiograms. On early CT (within 5 days) in 13 cases, blood was seen mainly or only in the cisterns around the midbrain. This pattern of hemorrhage was found in only 1 of 92 patients with a ruptured aneurysm. None of the unexplained perimesencephalic hemorrhages was associated with intracerebral hematoma or intraventricular hemorrhage. The clinical features also differed from those of aneurysmal hemorrhage; loss of consciousness was rare, and after 3 months, all 13 patients had returned to normal life. The cause of this benign disorder remains elusive, but a venous or capillary source seems likely.

Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage.

Using logistic regression, we analyzed the predictive value of a number of entry variables with respect to the outcome variables delayed cerebral ischemia, rebleeding, and poor outcome (death or severe disability) in patients with aneurysmal subarachnoid hemorrhage. The entry variables were clinical condition on admission (grades on the Glasgow Coma Scale, Hunt and Hess system), the amount of subarachnoid and intraventricular blood and the presence of hydrocephalus on the admission computed tomogram, and antifibrinolytic treatment with tranexamic acid. We used data from a prospectively studied population of 176 patients admitted within 72 hours after subarachnoid hemorrhage. The risk of delayed cerebral ischemia was best predicted by the amount of subarachnoid blood, intraventricular blood, and antifibrinolytic treatment irrespective of clinical condition and hydrocephalus. The site of delayed cerebral ischemia was not related to the location of the subarachnoid hemorrhage. Antifibrinolytic treatment was the only entry variable (negatively) predicting the risk of rebleeding. Death or severe disability after 3 months was best predicted by the amount of subarachnoid blood and the initial clinical condition reflected by the grade on the Glasgow Coma Scale.

Grading the amount of blood on computed tomograms after subarachnoid hemorrhage.

According to several studies, the amount of subarachnoid blood on the initial computed tomogram of patients with aneurysmal subarachnoid hemorrhage has predictive value with respect to infarction and outcome. Of several methods for assessing the amount of subarachnoid blood, none has been subjected to a study of interobserver agreement. We describe our own method, applied in previous studies, in which the amounts of blood in 10 basal cisterns and fissures and in four ventricles are graded separately. In grading single computed tomograms of 182 consecutive patients with subarachnoid hemorrhage, the agreement between pairs of three observers, studied with kappa statistics, was relatively good for individual cisterns or fissures (kappa between 0.35 and 0.65) and ventricles (kappa between 0.47 and 0.74). The Spearman rank correlation coefficients for the sum of the scores for subarachnoid and intraventricular blood were very high. Summed scores for extravasated blood are suitable as a baseline variable in follow-up studies of patients with subarachnoid hemorrhage.

Grading white matter lesions on CT and MRI: a simple scale.

We developed and tested a simple three-point scale for grading white matter lesions in anterior and posterior regions of the brain. Twenty four CT scans and 24 MRI scans were separately judged by 11 and five observers, respectively, on the presence and severity of white matter lesions. The observers were radiologists and neurologists. For CT scans, these periventricular changes were graded according to their extent as absent, or partly involving the white matter, or extending up to the subcortical region. The MRI lesions were graded as no lesion or only a single one, multiple focal lesions, and multiple confluent lesions. The pairwise agreements of all possible combinations of observers for each scan were corrected for chance (kappa statistics; maximal agreement 1.0). The weighted kappa value, for anterior and posterior regions combined, was 0.63 for CT scans, and 0.78 for MRI scans. This three-point scale for two separate regions seems suitable as a basis for cross-sectional or longitudinal studies of large series of patients.

Prognosis of coma after therapeutic hypothermia: A prospective cohort study

This study was designed to establish the reliability of neurologic examination, neuron‐specific enolase (NSE), and median nerve somatosensory‐evoked potentials (SEPs) to predict poor outcome in patients treated with mild hypothermia after cardiopulmonary resuscitation (CPR).

Management problems in acute hydrocephalus after subarachnoid hemorrhage.

In a consecutive series of 473 patients admitted within 72 hours after a subarachnoid hemorrhage, 91 (19%) had hydrocephalus on the initial computed tomogram. Consciousness was unimpaired in 25 of the 91 (28%). In 11 more patients acute hydrocephalus developed within 1 week after subarachnoid hemorrhage. Thirty-eight (8%) of all 473 patients subsequently showed clinical deterioration because of acute hydrocephalus; 11 of these 38 had fluctuations in the level of consciousness. Of the 66 patients with acute hydrocephalus and impaired consciousness on admission, 26 (39%) spontaneously improved within 24 hours. Ventricular drainage was performed in 32 (31%) of the 102 patients with acute hydrocephalus (7% of all 473 patients). Consciousness improved after ventricular drainage in 25 (78%) of the 32 patients. Ventriculitis developed in 12 of the 24 patients with external drainage, mainly after greater than 3 days of drainage, and in none of the eight patients with an internal shunt. Among the 340 patients with aneurysmal subarachnoid hemorrhage and no long-term tranexamic acid treatment, the frequency of rebleeding in patients with ventricular drainage (43% of 23) was significantly higher than in hydrocephalic patients without drainage (15% of 52 patients; chi 2 = 5.009, p = 0.025) and patients without acute hydrocephalus (20% of 265 patients; chi 2 = 5.521, p = 0.019). We conclude that spontaneous improvement occurs in half of the patients with acute hydrocephalus and impaired consciousness on admission, which is usually apparent within 24 hours, and that the outcome of patients who need ventricular drainage will improve if rebleeding and infection after insertion of the ventricular drain can be prevented.

Antifibrinolytic treatment in subarachnoid hemorrhage.

We enrolled 479 patients with subarachnoid hemorrhage in a multicenter, randomized, double-blind, placebo-controlled trial to determine whether treatment with the antifibrinolytic agent tranexamic acid improves outcome by preventing rebleeding. At three months there was no statistical difference between the outcomes in the tranexamic acid group and the control group. Of the 173 patients who died, 84 had received tranexamic acid and 89 placebo (95 per cent confidence interval for the difference in mortality rate, -6 to 11 per cent). Similarly, when analysis was restricted to patients with an angiographically demonstrated aneurysm, there was no significant difference between the groups. This absence of effect was not due to a lack of antifibrinolytic action, since the rate of rebleeding was reduced from 24 per cent in the control group to 9 per cent in the tranexamic acid-treated group (chi-square = 18.07, P less than 0.001), but resulted from a concurrent increase in the incidence of ischemic complications (15 per cent in the control group and 24 per cent in the tranexamic acid group; chi-square = 8.07, P less than 0.01). We conclude that until some method can be found to minimize ischemic complications, tranexamic acid is of no benefit in patients with subarachnoid hemorrhage.

Xanthochromia after subarachnoid haemorrhage needs no revisitation.

Recently it was contended that it is bloodstained cerebrospinal fluid (CSF) that is important in the diagnosis of subarachnoid haemorrhage (SAH) and not xanthochromia, and also that a normal CT scan and the absence of xanthochromia in the CSF do not exclude a ruptured intracranial aneurysm. The CSF findings were therefore reviewed of 111 patients with a proven SAH. All patients had xanthochromia of the CSF. Lumbar punctures were performed between 12 hours and one week after the ictus. Xanthochromia was still present in all (41) patients after 1 week, in all (32) patients after 2 weeks, in 20 of 22 patients after three weeks and in 10 of 14 patients after four weeks. In six years we identified only 12 patients with sudden headache, normal CT, bloodstained CSF, and no xanthochromia. Angiography was carried out in three and was negative. All 12 patients survived without disability and were not re-admitted with a SAH (mean follow up 4 years). It is concluded that it is still xanthochromia that is important in the diagnosis of SAH and not bloodstained CSF. Furthermore a normal CT scan and the absence of xanthochromia do exclude a ruptured aneurysm, provided xanthochromia is investigated by spectrophotometry and lumbar puncture is carried out between 12 hours and 2 weeks after the ictus.