Udo M. Illievich

Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhage

OBJECTIVE To analyze the influence of extracerebral organ system dysfunction after aneurysmal subarachnoid hemorrhage (SAH) on mortality and neurologic outcome. DESIGN Observational study with retrospective data extraction. SETTING Neurosurgical intensive care unit (NICU) at a primary level university hospital, supervised and staffed by both members of the Clinic of Neurosurgery and the Clinic of Anesthesiology and General Intensive Care. PATIENTS Two hundred forty-two patients treated for intracranial aneurysm rupture within 7 days of the most recent SAH. INTERVENTIONS Routine neurosurgical interventions for obliteration of the ruptured aneurysm (microsurgery, Guglielmi Detachable Coils embolization) and for treatment of posthemorrhagic hydrocephalus (ventriculostomy, cerebrospinal fluid shunt implantation). MEASUREMENTS AND MAIN RESULTS Respiratory, renal, hepatic, cardiovascular, and hematologic organ system functions were evaluated both individually and in aggregate by using a modified version of the Multiple Organ Dysfunction (mMOD) score. Of 1,452 organ system functions assessed in 242 patients during their NICU stay, 714 organ system functions were intact (cerebral: 0, extracerebral: 714), 556 organ systems had mild-to-moderate dysfunctions (mMOD scoremax 1-2 for the affected organ system; cerebral: 153, extracerebral: 403), and 182 organ systems failed (mMOD scoremax 3 for the affected organ system; cerebral: 89, extracerebral: 93). Severity of extracerebral organ system dysfunctions correlated with the degree of neurologic impairment (Hunt and Hess [H&H] score) in a graded fashion. Similarly, the chance to develop systemic inflammatory response syndrome (SIRS) during the NICU stay increased with increasing admission H&H grade. The incidence of SIRS and septic shock was 29% and 10.3%, respectively. The mortality rate was 40.2% in patients with SIRS and 80% for patients suffering septic shock. Seventy-seven percent of extracerebral organ system failures (OSFs) occurred in conjunction with SIRS: 51% of respiratory OSFs, 97% of renal OSFs, 100% of hepatic OSFs, 96% of cardiovascular OSFs, and 73% of hematopoietic OSFs. Both CNS dysfunction and extracerebral organ system dysfunctions were significantly related to neurologic outcome. The probability of unfavorable neurologic outcome significantly increased with both decreasing cerebral perfusion pressure (CPP) and increasing severity of extracerebral organ dysfunction. CONCLUSION Aneurysmal SAH and its neurologic sequelae accounted for the principal morbidity and mortality in the current series. Development of extracerebral organ system dysfunction was associated with a higher probability of unfavorable neurologic outcome. Systemic inflammation (SIRS) and secondary organ dysfunction were the principal non-neurologic causes of death.

Effects of hypothermia or anesthetics on hippocampal glutamate and glycine concentrations after repeated transient global cerebral ischemia.

BackgroundThe search for cerebroprotective pharmacologic interventions has been based on the assumption that reducing the cerebral metabolic rate may enhance the cerebral tolerance for ischemic episodes. Recently, evidence has accumulated implicating excitatory amino acids (e.g., glutamate) as mediators of ischemic brain injury. We investigated the effects of mild hypothermia (32° C), pentobarbital, isoflurane, and propofol on hippocampal extracellular concentrations of glutamate and glycine after repeated global ischemia. MethodsNew Zealand white rabbits were initially anesthetized with halothane in oxygen. Brain epidural temperature was reduced by external cooling in the hypothermia group to 32° C (n = 5). A burst-suppressed electroencephalogram pattern was achieved in the other groups with isoflurane (n = 7), pentobarbital (n = 6), or propofol (n = 6). Halothane-anesthetized rabbits (1% inspired) served as the control group (n = 5). In all groups, two global cerebral ischemic episodes (each 7.5 min) were produced by a combination of neck tour niquet inflation and induction of systemic hypotension. Perlischemic hippocampal glutamate and glycine concentrations were estimated using in vivo microdialysis and high-performance liquid chromatography (two-way analysis of variance, P < 0.05). ResultsGlutamate concentrations were similar in the five groups during the baseline period. Hypothermia (32° C) was associated with significantly lower concentrations of glutamate during both the first and second ischemic periods when compared with all other groups. Although there were no differences in glycine concentrations among groups during the first ischemic episode, glycine concentrations were significantly lower in the hypothermic group compared with the control, isoflurane, and pentobarbital groups during the second episode of cerebral ischemia. Glycine concentrations also were lower in the propofol group when compared to the isoflurane and pentobarbital groups. ConclusionsHypothermia (32° C) attenuates ischemia-induced increases in both glutamate and glycine concentrations after repeated global cerebral ischemia. Propofol attenuated glycine increases in a manner similar to that of hypothermia but did not attenuate ischemia-induced glutamate increases. There were no differences in hippocampal glutamate or glycine concentrations for animals receiving isoflurane, halothane, or pentobarbital.

Prone position in subarachnoid hemorrhage patients with acute respiratory distress syndrome: effects on cerebral tissue oxygenation and intracranial pressure.

OBJECTIVE To analyze the effect of prone position on cerebral perfusion pressure and brain tissue oxygen partial pressure in subarachnoid hemorrhage patients with acute respiratory distress syndrome (ARDS). DESIGN Clinical study with retrospective data analysis. SETTING Neurosurgical intensive care unit of a primary level university hospital. PATIENTS Sixteen patients treated for intracranial aneurysm rupture with initial Hunt and Hess grade III or worse who developed ARDS within 2 wks after the bleeding. INTERVENTIONS Routine neurosurgical intensive care treatment for subarachnoid hemorrhage and posthemorrhagic vasospasm including cerebral monitoring with continuous intracranial pressure and brain tissue oxygen partial pressure recordings. MEASUREMENTS AND MAIN RESULTS Hemodynamics, arterial oxygenation, ventilatory setting, intracranial pressure, cerebral perfusion pressure, and brain tissue oxygen partial pressure in the supine as well as in the prone position were analyzed and compared. A significant increase in Pao(2) from 97.3 +/- 20.7 torr (mean +/- sd) in the supine position to 126.6 +/- 31.7 torr in the prone position was joined by a significant increase in brain tissue oxygen partial pressure from 26.8 +/- 10.9 torr to 31.6 +/- 12.2 torr (both p <.0001), whereas intracranial pressure increased from 9.3 +/- 5.2 mm Hg to 14.8 +/- 6.7 mm Hg and cerebral perfusion pressure decreased from 73.0 +/- 10.5 mm Hg to 67.7 +/- 10.7 mm Hg (both p <.0001). CONCLUSIONS The beneficial effect of prone positioning on cerebral tissue oxygenation by increasing arterial oxygenation appears to outweigh the expected adverse effect of prone positioning on cerebral tissue oxygenation by decreasing cerebral perfusion pressure in ARDS patients.

Awake nasotracheal fiberoptic intubation: patient comfort, intubating conditions, and hemodynamic stability during conscious sedation with remifentanil.

Awake nasotracheal fiberoptic intubation requires an anesthetic management that provides sufficient patient comfort, adequate intubating conditions, and stable hemodynamics. Short-acting and easily titratable analgesics are excellent choices for this maneuver. In this study, our aim was to determine an appropriate dosage regimen of remifentanil for awake nasotracheal fiberoptic intubation. For that reason, we compared two different dosage regimens. Twenty-four patients were randomly assigned to receive remifentanil 0.75 &mgr;g/kg in bolus, followed by a continuous infusion of 0.075 &mgr;g · kg−1 · min−1 (Group L), or remifentanil 1.5 &mgr;g/kg in bolus, followed by a continuous infusion of 0.15 &mgr;g · kg−1 · min−1 (Group H). All patients were premedicated with midazolam 0.05 mg/kg IV and glycopyrrolate 0.2 mg IV. Both dosage regimens ensured patient comfort and sedation. Discomfort did not differ between groups. Patients in Group H were sedated more profoundly. Hemodynamic stability was maintained with both remifentanil doses. Intubating conditions were adequate in all patients and comparable between the groups. The large dosage regimen did not result in any additional benefit compared with the small dosage. For awake nasotracheal fiberoptic intubation, we therefore recommend remifentanil 0.75 &mgr;g/kg in bolus followed by continuous infusion of 0.075 &mgr;g · kg−1 · min−1, supplemented with midazolam 0.05 mg/kg.

Temporal artery versus bladder thermometry during perioperative and intensive care unit monitoring.

BACKGROUND:Core temperature measurements are an important component of perioperative patient monitoring. It is fairly easy to obtain core temperature measurements invasively in anesthetized patients. However, such measurements are more difficult to obtain noninvasively in awake patients. Recently, a new version of a temporal artery thermometer for noninvasive core temperature measurements (TemporalScanner™ TAT-5000) was introduced with accuracy and precision advertised as being comparable to invasive core temperature measurements. In this study, we sought to determine if this new thermometer is an acceptable substitute for invasive bladder temperature measurement. METHODS:In 35 patients undergoing neurosurgical interventions and 35 patients in the neurosurgical intensive care unit, measurements from the temporal artery thermometer were compared with those from a bladder thermometer. Four measurements were obtained from each patient. RESULTS:Overall 280 measurement pairs were obtained. The mean bias between the methods was 0.07°C ± 0.79°C; the limits of agreement were ≈3 times greater than the a priori defined limit of ±0.5°C (−1.48 to 1.62). The sensitivity for detecting fever (core temperature >37.8°C) using the temporal artery thermometer was 0.72, and the specificity was 0.97. The positive predictive value for fever was 0.89; the negative predictive value was 0.94. The sensitivity for detecting hypothermia (core temperature <35.5°C) was 0.29, and the specificity was 0.95. The positive predictive value for hypothermia was 0.31, and the negative predictive value was 0.95. CONCLUSIONS:The results of this study do not support the use of temporal artery thermometry for perioperative core temperature monitoring; the temporal artery thermometer does not provide information that is an adequate substitute for core temperature measurement by a bladder thermometer.

Changes in oxygenation variables during progressive hypothermia in anesthetized patients.

Summary Because deliberate hypothermia is becoming commonly used during neurosurgery, this study was performed to investigate the effects of a progressive reduction of body core temperature (T) on whole body oxygenation variables in patients undergoing elective intracranial surgery. In 13 patients (Hypothermic Group), T was reduced to 32.0°C using convective-based surface cooling. In six patients (Control Group), T was maintained at 35.5°C during the entire study period. The cardiac index (CI) was determined with a pulmonary artery catheter by thermodilution. Whole body oxygen delivery (DO2) was calculated from CI and arterial oxygen content. Whole body oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (EE) were determined by ventilation gas analysis (indirect calorimetry). Mixed venous oxygen tension at 50% saturated hemoglobin (P50), and whole body oxygen extraction ratio (O2ER) were calculated. Repeated-measures analysis of variance and the Mann-Whitney test were used for statistical analysis. Data are expressed as means ± SD. VO2 (from 100 ± 13 to 77 ± 11 ml · min-1 ± m-2), VCO2 (from 75 ± 7 to 57 ± 7 ml min-1 ± m-2), EE (from 667 ± 67 to 509 ± 66 kcal ± d-1 · m-2), P50 (from 23.8 ± 1.7 to 20 ± 0.9 mm Hg), and O2ER (from 0.29 ± 0.05 to 0.22 ± 0.03%) decreased significantly in the Hypothermic Group between 35.5 and 32.0°C (p < 0.05). None of these variables changed in the Control Group and at 32.0°C VO2, VCO2, EE, P50, and O2ER were significantly lower in the Hypothermie Group than in the Control Group. DO2 remained unchanged in both groups. We conclude that progressive hypothermia in anesthetized patients reduces metabolic rate but does not change DO2. The significant decrease in O2ER may partly be related to a leftward shift of the oxyhemoglobin dissociation curve, as evidenced by the decrease in P50.

The cerebral and cardiovascular effects of cisatracurium and atracurium in neurosurgical patients.

Drugs for neurosurgical patients should not increase intracranial pressure (ICP) or change cerebral perfusion pressure (CPP) and cerebral blood flow.This double-blind, cross-over study compares the effects of a single (3 x effective dose producing 95% twitch depression) intravenous bolus dose of cisatracurium 0.15 mg/kg with atracurium 0.75 mg/kg on mean red blood cell flow velocity in the middle cerebral artery (CBFV; transcranial Doppler), ICP (intraventricular or intraparenchymal monitor), mean arterial pressure (MAP), CPP (MAP - ICP), and heart rate (HR) every minute during a 15-min study period. Included in the study were 14 sedated and ventilated adult neurosurgical patients. After the cisatracurium bolus, ICP, CPP, CBFV, MAP, and HR did not change, and no histamine related events were observed. After the atracurium bolus, ICP, CPP, CBFV, and MAP decreased. The lowest values of ICP (-16% of baseline), CPP (-5%), CBFV (-8%), and MAP (-7%) were recorded 2-4 min after the atracurium bolus injection. After this transient decrease, MAP and CPP returned to baseline, whereas CBFV and ICP transiently exceeded baseline values. The highest values of CBFV (5%) and ICP (17%) were recorded 9-12 min after the atracurium bolus injection. Five patients showed a typical histamine response after atracurium, with a decrease in MAP and flushing. Excluding these five patients eliminated statistical significance in ICP, CPP, CBFV, and MAP differences. In conclusion, cisatracurium demonstrated fewer cerebral and cardiovascular hemodynamic side effects in sedated adult neurosurgical patients. Implications: This double-blind study in sedated and mechanically ventilated adult neurosurgical patients demonstrates that an intravenous bolus dose of the neuromuscular blocker cisatracurium results in less cerebral (intracranial pressure, cerebral perfusion pressure, middle cerebral artery blood flow velocity) and cardiovascular (blood pressure) hemodynamic side effects, compared with an equipotent dose of atracurium.

Electroencephalographic burst suppression by propofol infusion in humans : hemodynamic consequences

The hemodynamic effects of a propofol infusion adjusted to achieve and maintain a burst-suppression pattern [episodes of depressed background activity (electrical silence) more than 4 s alternating with a high-voltage slow activity], were studied in 10 patients without cardiorespiratory disease undergoing elective neurosurgical interventions. Propofol infusion was started after a bolus dose of 1 mg/kg at a rate of 20 mg.kg-1 x h-1, reduced after 30 min to 15 mg.kg-1 x h-1, and terminated after 60 min (1926 +/- 346 mg cumulative propofol dose, maximal serum concentration 9.2 +/- 2.9 micrograms/dL; mean +/- SD). Hemodynamic data and arterial blood samples were collected during a sedated, resting control period, and then every 15 min during drug infusion. Lactated Ringers solution was infused at a rate sufficient to maintain pulmonary capillary wedge pressure at or above control levels (20-30 mL.kg-1 x h-1). Burst-suppression pattern in the electroencephalogram was achieved after 15.7 +/- 3.2 min and maintained until 10.9 +/- 2.6 min after the propofol infusion was terminated. Significant decreases (% of control, Friedman and Wilcoxon Wilcox test, P < 0.05) were found in heart rate (19%), mean arterial pressure (20%), cardiac index (23%), and left ventricular stroke work index (26%). No adverse consequences were caused by the propofol or crystalloid infusion. The results demonstrate that doses of propofol sufficient to silence the electroencephalogram are associated with venodilating and myocardial depressant properties. However, propofol can be administered with minimal hemodynamic risk in healthy patients when cardiac filling pressures are maintained by intravenous fluid administration.

High-dose Remifentanil Does Not Impair Cerebrovascular Carbon Dioxide Reactivity in Healthy Male Volunteers

Background Cerebrovascular carbon dioxide reactivity during high-dose remifentanil infusion was investigated in volunteers by measurement of regional cerebral blood flow (rCBF) and mean CBF velocity (CBFv). Methods Ten healthy male volunteers with a laryngeal mask for artificial ventilation received remifentanil at an infusion rate of 2 and 4 &mgr;g · kg−1 · min−1 under normocapnia, hypocapnia, and hypercapnia. Stable xenon-enhanced computed tomography and transcranial Doppler ultrasonography of the left middle cerebral artery were used to assess rCBF and mean CBFv, respectively. If required, blood pressure was maintained within baseline values with intravenous phenylephrine to avoid confounding effects of altered hemodynamics. Results Hemodynamic parameters were maintained constant over time. Remifentanil infusion at 2 and 4 &mgr;g · kg−1 · min−1 significantly decreased rCBF and mean CBFv. Both rCBF and mean CBFv increased as the arterial carbon dioxide tension increased from hypocapnia to hypercapnia, indicating that cerebrovascular reactivity remained intact. The average slopes of rCBF reactivity were 0.56 ± 0.27 and 0.49 ± 0.28 ml · 100 g−1 · min−1 · mmHg−1 for 2 and 4 &mgr;g·kg−1·min−1 remifentanil, respectively (relative change in percent/mmHg: 1.9 ± 0.8 and 1.6 ± 0.5, respectively). The average slopes for mean CBFv reactivity were 1.61 ± 0.95 and 1.54 ± 0.83 cm · s−1 · mmHg−1 for 2 and 4 &mgr;g · kg−1 · min−1 remifentanil, respectively (relative change in percent/mmHg: 1.86 ± 0.59 and 1.79 ± 0.59, respectively). Preanesthesia and postanesthesia values of rCBF and mean CBFv did not differ. Conclusion High-dose remifentanil decreases rCBF and mean CBFv without impairing cerebrovascular carbon dioxide reactivity. This, together with its known short duration of action, makes remifentanil a useful agent in the intensive care unit when sedation that can be titrated rapidly is required.

The arterial to end-tidal carbon dioxide gradient increases with uncorrected but not with temperature-corrected Paco2 determination during mild to moderate hypothermia

End-tidal carbon dioxide (PETCO2) monitoring is recommended as a basic standard of care and is helpful in adjusting mechanical ventilation. Gas solubility changes with temperature, which might affect the PaCO2 and thereby the gradient between Paco2 and PETCO2 (PA-ETCO2) under hypothermic conditions. We investigated whether the PA-ETCO2 changes during mild to moderate hypothermia (36[degree sign]C-32[degree sign]C) using PaCO2 measured at 37[degree sign]C (uncorrected PaCO2) and PaCO2 corrected to actual body temperature. We preoperatively investigated 19 patients. After anesthesia had been induced, controlled ventilation was established to maintain normocarbia using constant uncorrected PaCO (2) to adjust ventilation (alpha-stat acid-base regimen). Body core temperature was reduced without surgical intervention to 32[degree sign]C by surface cooling. Continuous PETCO2 was monitored with a mainstream PETCO2 module. The PA-ETCO (2) was calculated using the uncorrected and corrected PaCO2 values. During body temperature reduction from 36[degree sign]C to 32[degree sign]C, the gradient between PETCO2 and uncorrected PaCO2 increased 2.5-fold, from 4.1 +/- 3.7 to 10.4 +/- 3.8 mm Hg (P < 0.002). The PA-ETCO2 remained unchanged when the corrected Paco2 was used for the calculation. We conclude that when the alpha-stat acid-base regimen is used to adjust ventilation, the PA-ETCO2 calculated with the uncorrected PaCO2 increases and should be added to the differential diagnosis of widened PA-ETCO2. In contrast, when the corrected PaCO2 is used for the calculation of the PA-ETCO2, the PA-ETCO2 remains unaltered during hypothermia. Implications: We investigated the impact of induced hypothermia (36[degree sign]C-32[degree sign]C) on the gradient between PaCO2 and PETCO2 (PA-ETCO (2)). The PA-ETCO2 increased 2.5-fold when CO2 determinations were not temperature-corrected. Hypothermia should be added to the differential diagnosis of an increased PA-ETCO2 when the alpha-stat acid-base regimen is used. (Anesth Analg 1998;86:1131-6)