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Repetitive synchronized cyclical oscillations of multisystem parameters subsequent to high-dose thiopental therapy for status epilepticus secondary to herpes encephalitis

2000; Elsevier BV; Volume: 85; Issue: 3 Linguagem: Inglês

10.1093/bja/85.3.471

1471-6771

I.R. Ghosh, R.M. Langford, Katri Nieminen, A. Kari, Jukka Takala,

Epilepsy research and treatment

We report a case of status epilepticus secondary to herpes encephalitis, treated with thiopental infusion and mechanical ventilation. The computerized storage and analysis of physiological data led to the detection of repetitive synchronized cyclical oscillations of arterial pressure, heart rate, EEG parameters, peripheral temperature and core temperature. Arterial pressure oscillations have been described in patients who are severely systemically unwell; cardiovascular and brain electrical activity may also oscillate in the presence of raised intracranial pressure. In contrast, this patient had no features of severe systemic illness or of raised intracranial pressure. Our hypothesis is that high-dose thiopental may have been a cause of our findings by producing autonomic dysfunction. We report a case of status epilepticus secondary to herpes encephalitis, treated with thiopental infusion and mechanical ventilation. The computerized storage and analysis of physiological data led to the detection of repetitive synchronized cyclical oscillations of arterial pressure, heart rate, EEG parameters, peripheral temperature and core temperature. Arterial pressure oscillations have been described in patients who are severely systemically unwell; cardiovascular and brain electrical activity may also oscillate in the presence of raised intracranial pressure. In contrast, this patient had no features of severe systemic illness or of raised intracranial pressure. Our hypothesis is that high-dose thiopental may have been a cause of our findings by producing autonomic dysfunction. An 18-yr-old male with no history of epilepsy was treated in the emergency unit for status epilepticus. There were no focal neurological signs or evidence of raised intracranial pressure. Seizure activity persisted despite cumulative total doses of phenytoin 1500 mg and diazepam 60 mg. A loading dose of thiopental 1000 mg was therefore given followed by tracheal intubation and mechanical ventilation. Positive herpes zoster antibody serology and cerebrospinal fluid polymerase chain reaction studies later confirmed the diagnosis of viral encephalitis. On admission to the intensive care unit (ICU), intermittent positive-pressure ventilation was continued, together with a thiopental infusion titrated up to 500 mg h−1 under the guidance of a continuously running paper electroencephalogram (EEG), which confirmed the presence of burst suppression and the absence of seizure activity. Standard monitoring included continuous electrocardiography (ECG), invasive arterial pressure, capnography, respiratory flow/volume measurements, hourly urine output measurements and repeated arterial blood gas analysis. The cardiorespiratory, haematological, hepatic, renal, biochemical and blood gas profiles were within normal limits. In particular, no signs of poor tissue oxygenation or pH imbalance were observed. Cranial CT and MRI scans showed no abnormalities. Additional therapy included acyclovir 750 mg 8-hourly and a crystalloid infusion at 100–250 ml h−1. No sympathomimetic therapy was required. No subsequent seizures were detected clinically or electroencephalographically, and the thiopental infusion was stopped on day 2, by which time the patient had received 7975 mg over 20 h. Regular intravenous phenytoin therapy (250 mg 12-hourly) was continued. On day 3, with the relatives' assent and research ethics committee approval, specialized monitoring was set up as part of the EU Biomed 1 IMPROVE intensive care project1Carson E Saranummi N Improving control of patient status in critical care: the IMPROVE project.Comp Methods Prog Biomed. 1996; 51: 1-130Abstract Full Text PDF Google Scholar in order to establish an annotated data library. This involved acquiring and storing continuous physiological variables (including arterial pressure, ECG and capnographs at sampling rates between 25 and 100 Hz) and intermittent annotations (exact timing of drug doses, insertion of lines and any other interventions). This period of specialized monitoring lasted 24 h, during which time continuous digitized EEG was also recorded.2Thomsen CE Gade J Nieminen K Langford RM Ghosh IR Jensen K et al.Collecting EEG Signals in the IMPROVE Data Library.IEEE Eng Med Biol. 1997; 16: 33-40Crossref PubMed Scopus (17) Google Scholar No notable clinical events occurred in this 24 h period, and biochemical and blood gas profiles remained within normal limits. As on admission, there were no signs of raised intracranial pressure. Subsequently, the patient made an uncomplicated recovery; his level of consciousness improved and the tracheal tube was removed on day 6. At this point his Glasgow Coma Scale score was 15 and gross intellectual functions were normal. He left the ICU on day 7 and went home on day 14. Retrospective trend analysis revealed marked cyclical oscillations of the multisystem physiological variables over 24 h (Fig. 1). Assessments were made of raw data (peripheral and core temperature, mean arterial pressure, heart rate) and frequently used processed EEG parameters. The latter consisted of root mean squared amplitude (each EEG amplitude digital value within a sampling period is squared, a mean is subsequently taken and the square root of this is taken) and median power frequency (frequency at which half the spectral power is above and half is below). Peaks of relative hypertension occurred synchronously with peaks in EEG amplitude. Oscillations in heart rate and EEG frequency both showed a close inverse relationship to arterial pressure and EEG amplitude. Peripheral temperature and urine output also showed oscillations, though these did not show exact synchrony with the other parameters. The variability of physiological parameters is an important indicator used in assessment and prediction in intensive care patients. Several types of variability have been observed: the simplest example is the ECG R–R interval, which is a good measure of (i) reactivity to stress during critical illness and (ii) autonomic neuropathy. Similarly, EEG reactivity to stimuli carries the same implications; the presence of reactivity is reassuring, and the lack of reactivity (in the absence of drug-induced or hypothermic coma) suggests a poor prognosis.3Synek VM Prognostically important EEG coma patterns in diffuse anoxic and traumatic encephalopathies in adults.J Clin Neurophysiol. 1988; 5: 161-174Crossref PubMed Scopus (192) Google Scholar More orderly variations exist in both cardiac and neurological signals. First-, second-, third- and, more recently, fourth-order blood-pressure waves have been described and summarized elegantly by Seiver and colleagues.4Seiver A Daane S Kim R Regular low frequency cardiac output oscillations observed in critically ill surgical patients.Complexity. 1997; 2: 51-55Crossref Scopus (9) Google Scholar First- and second-order waves are descriptions of blood-pressure variations with each systolic beat and respiratory cycle, respectively. Third-order waves, with a cycle of 10–160 s, are a consequence of disordered autonomic feedback. Fourth-order waves (cycles of minutes to hours, as seen in this case) have been thought to be due to poor oxygen delivery to the tissues and are associated with a poor prognosis.4Seiver A Daane S Kim R Regular low frequency cardiac output oscillations observed in critically ill surgical patients.Complexity. 1997; 2: 51-55Crossref Scopus (9) Google Scholar 5Carroll G Fourth-order blood pressure waves.J Am Med Assoc. 1990; 236: 856Crossref Scopus (6) Google Scholar Electroencephalographers have described cyclical changes in association with sleep patterns;6Loomis AL Harvey EN Hobart G Potential rhythms of the cerebral cortex during sleep.Science. 1938; 81: 589-597Google Scholar the presence or absence of these features has, in turn, relevance to prognostication in coma.7Chatrian GE White LE Daly D Electroencephalographic patterns resembling those of sleep in certain comatose states after injuries to the head.Electroencephalogr Clin Neurophysiol. 1963; 15: 272-279Abstract Full Text PDF PubMed Scopus (108) Google Scholar 8Evans BM Bartlett JR Prediction of outcome in severe head injury based on recognition of sleep related activity in the polygraphic electroencephalogram.J Neurol Neurosurg Psychiatry. 1995; 59: 17-25Crossref PubMed Scopus (63) Google Scholar Repetitive waves with cycling of minutes to hours are also seen in the EEG monitoring of patients with brain insult as a consequence of raised intracranial pressure.9Munari C Calbucci F Correlations between intracranial pressure and EEG during coma and sleep.Electroencephalogr Clin Neurophysiol. 1981; 51: 170-176Abstract Full Text PDF PubMed Scopus (30) Google Scholar In this case, we considered three possible causes of the multiparameter oscillations. Classical fourth-order changes seemed unlikely, as severe systemic dysfunction was not evident. Covertly raised intracranial pressure may have been an alternative cause, though there was never any clinical or radiological evidence of it, or of persisting brain injury. Lastly, we could not exclude high-dose thiopental infusion as an important cause. Plasma levels were not measured, as these findings became apparent only on trend analysis after the cessation of monitoring. Our hypothesis is that high-dose thiopental may cause autonomic dysfunction, leading to loss of 'randomicity'; this would be similar to the hypothesis of fourth-order oscillations caused by poor tissue oxygen delivery in ill patients. The interesting phenomenon of synchronized cyclical oscillations of physiological parameters should not automatically instil concern, and may prove to be a recognized finding when high-dose thiopental infusion is used or there is covert brain dysfunction. This may, in time, be clarified with the increasing sophistication of polygraphic trend analysis in intensive care, without which our findings would not have been apparent. To validate these findings, prospective studies of high-dose thiopental infusions (including the simultaneous measurement of plasma levels) and intracranial pressure monitoring should be encouraged. We acknowledge the help of the Kuopio ICU staff and the loan of equipment from Aalborg University and St Bartholomew's Hospital, London (Anaesthetics Laboratory and Clinical Neurophysiology Department).