This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schwab, S. Articles by Hacke, W. Search for Related Content PubMed PubMed Citation Articles by Schwab, S. Articles by Hacke, W.

(Stroke. 1998;29:2461-2466.)
© 1998 American Heart Association, Inc.

Original Contributions

Moderate Hypothermia in the Treatment of Patients With Severe Middle Cerebral Artery Infarction

S. Schwab, MD; S. Schwarz, MD; M. Spranger, MD; E. Keller, MD; M. Bertram, MD W. Hacke, MD

From the Department of Neurology, University of Heidelberg, Heidelberg, Germany.

Correspondence to Stefan Schwab, MD, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. E-mail Stefan_Schwab{at}ukl.uni_heidelberg.de

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose—Animal research and clinical studies in head trauma patients suggest that moderate hypothermia may improve outcome by attenuating the deleterious metabolic processes in neuronal injury. Clinical studies on moderate hypothermia in the treatment of acute ischemic stroke patients are still lacking.

Methods—Moderate hypothermia was induced in 25 patients with severe ischemic stroke in the middle cerebral artery (MCA) territory for therapy of postischemic brain edema. Hypothermia was induced within 14±7 hours after stroke onset and achieved by external cooling with cooling blankets, cold infusions, and cold washing. Patients were kept at 33°C body-core temperature for 48 to 72 hours, and intracranial pressure (ICP), cerebral perfusion pressure, and brain temperature were monitored continuously. Outcome at 4 weeks and 3 months after the stroke was analyzed with the Scandinavian Stroke Scale (SSS) and Barthel index. The side effects of induced moderate hypothermia were analyzed.

Results—Fourteen patients survived the hemispheric stroke (56%). Neurological outcome according to the SSS score was 29 (range, 25 to 37) 4 weeks after stroke and 38 (range 28 to 48) 3 months after stroke. During hypothermia, elevated ICP values could be significantly reduced. Herniation caused by a secondary rise in ICP after rewarming was the cause of death in all remaining patients. The most frequent complication of moderate hypothermia was pneumonia in 10 of the 25 patients (40%). Other severe side effects of hypothermia could not be detected.

Conclusions—Moderate hypothermia in the treatment of severe cerebral ischemia is not associated with severe side effects. Moderate hypothermia can help to control critically elevated ICP values in severe space-occupying edema after MCA stroke and may improve clinical outcome in these patients.

Key Words: hypothermia • intracranial pressure • neuroprotection • outcome • stroke, ischemic • treatment

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The neuroprotective effect of profound hypothermia has long been recognized, but use of hypothermia for the therapy of neuronal injuries was abandoned because of management problems and severe side effects, such as cardiac arrhythmia, shivering, infections, and coagulation disorders.¹ In the past decade, it has come to be recognized that even mild (34°C to 36°C) or moderate (34°C to 28°C) therapeutic modulation of temperature may substantially avert brain damage caused by ischemia in both experimental stroke and other neuronal injuries.^{2 3} After focal cerebral ischemia, hypothermia reduced infarct volumes up to 90%,^{4 5 6} whereas hyperthermia had a significantly negative effect on histopathological findings and outcome.^{7 8 9}

The mechanisms by which hypothermia is neuroprotective are not fully understood yet. Hypothermia, however, was found to reduce cerebral metabolism, decrease levels of excitatory amino acids, stabilize the blood-brain barrier, and account for membrane stabilization and the decrease in heat shock proteins after induced brain injury.^{10 11 12}

Several clinical studies reported the effects of hypothermia in the therapy of traumatic brain injury.^{13 14 15 16} All demonstrated that mild to moderate hypothermia has the potential to limit the extent of secondary brain injury and may be effective in the treatment of patients with severe traumatic head injury.

Even though hypothermia has potent cerebroprotective effects after experimental focal ischemia, clinical studies on hypothermic therapy after middle cerebral artery (MCA) infarction are not available. However, 2 recent clinical studies emphasized the importance of body temperature for stroke prognosis and severity.^{17 18} Reith et al¹⁸ demonstrated lower mortality and better outcome in patients with mild hypothermia (<36.5°C) on admission. Azzimondi et al¹⁷ showed that fever in the first 7 days after stroke was an independent predictor of poor outcome.

We performed an open pilot study on the efficacy, feasibility, and safety of induced moderate hypothermia in the therapy of patients with acute, severe MCA infarction and increased intracranial pressure (ICP).

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
This study is based on 25 patients, 18 men and 7 women (age, 35 to 72 years; mean, 49±14 years), who had suffered acute severe MCA-territory stroke and were admitted to the neurocritical care unit for treatment of elevated (ICP. The study was approved by the local ethics committee. Inclusion criteria were clinical and computed tomographic evidence of acute, large, complete MCA infarction (which consisted of early large parenchymal hypodensity and signs of local brain swelling, such as sulci effacement and lateral ventricle compression); further neurological deterioration compared with the baseline clinical status on admission to the neurocritical care unit; and control computed tomography at that time showing complete MCA infarction with an increased space-occupying effect with compression of the lateral ventricle beginning midline shift and compression of the basal cisterns. Patients with any previous disabling neurological diseases or terminal illnesses were excluded from this protocol.

The ICP was monitored in all patients with 2 different types of intraparenchymatous sensors and transducers (Spiegelberg pneumatic transducer, Spiegelberg AG, n=16; Codman microsensor, Johnson & Johnson, n=9). ICP devices were inserted ipsilaterally to the affected hemisphere in 18 patients and bilaterally in 7 patients. Clinical data were obtained daily from all patients and assessed with the Scandinavian Stroke Scale (SSS) and Glasgow Coma Scale (GCS).^{19 20} Clinical outcome was assessed 4 weeks and 3 months after stroke with the 58-point SSS and the Rankin scale. Daily living activities were rated with the 100-point Barthel index (BI).^{21 22}

General Critical Care
The focus of critical care for all patients was to maintain cerebral perfusion pressure (CPP) above 70 mm Hg. CPP was calculated as the difference between mean arterial blood pressure and ICP. To reach mean arterial blood levels >90 mm Hg, vasopressors (norepinephrine 0.2 µg · kg^-1 · min^-1) were used. Hemoglobin concentration was maintained at >90 g/L. Patients with increased ICP (>20 mm Hg) were treated with intermittent boluses of mannitol (0.5 to 1 g/kg) before initiation of hypothermia. Hyperventilation or barbiturates were not part of our treatment regimen. In 7 patients, an optimetric jugular bulb catheter for cerebrovenous oxygen saturation monitoring (Opticath, Abbott Laboratories) was inserted. Monitoring in the neurocritical care unit always consisted of continuous monitoring of ICP, CPP, ECG, end-expiratory PCO₂, and blood pressure. We adjusted ventilatory parameters to a PO₂ of >90 mm Hg and a PCO₂ between 35 and 40 mm Hg (ie, by increasing positive end-expiratory pressure or FiO₂).

Temperature Protocol
Brain temperature was measured with the Spiegelberg intraparenchymatous ICP probe, which has a thermistor in its tip. Accuracy for temperature measurements is <0.1°C. A Foley temperature catheter for bladder temperature reading with a temperature resolution of 0.1°C was used for monitoring body-core temperature (Mon-a-therm, Mallinckrodt). All patients were sedated with fentanyl and propofol and received neuromuscular blockade with continuous infusion of atracurium (0.3 to 0.6 mg/kg IV).

Room temperature in the intensive care unit was between 18°C and 20°C. In this study, a cooling blanket (Polar Bair, Augustine Medical) with cool ventilator air fanning the patient's body surface was used for external cooling. Acid-base management was guided by blood-gas analysis not corrected for temperature to maintain autoregulation (-stat management).²³ Once the body-core temperature reached 33°C, it was kept between 33°C and 34°C for 48 to 72 hours. During the next 24 hours, the patient was passively rewarmed to a normal temperature.

Evaluation of Side Effects
Side effects known to be related to hypothermia, such as infections, coagulation disorders, and decreased cardiac performance with bradycardia, cardiac arrhythmia, and hypotension, were documented and analyzed. Sepsis as a systemic response to infection was suspected, according to the criteria of the American College of Chest Physicians, when 2 of the following conditions became manifest: heart rate >90 bpm, white blood cell count >12 000 or <4000 cells/mm³, respiratory rate >20 breaths per minute, or PaCO₂ <32 mm Hg. Body temperature as 1 further point was not analyzed.²⁴ Pneumonia was suspected if the following criteria were met: new infiltrates on chest x-ray, purulent tracheobronchial secretions, and impairment of pulmonary gas exchange. Renal function was evaluated by urine output and creatinine clearance. Activated prothrombin and partial thromboplastin times were measured every 6 hours to evaluate intrinsic and extrinsic coagulation pathways. Platelet counts, serum enzymes, and electrolytes were determined every 12 hours.

Statistics
All values are expressed as mean±SD. Median is also given for ordinal data, such as SSS and BI. Physiological measurements within groups were analyzed by nonparametric tests as appropriate (Wilcoxon signed-rank test). Significance was assigned at P<0.05.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patients
On admission, the median SSS score was 24 (range, 18 to 28); the mean GCS was 9 (range, 4 to 13). All patients presented with severe dense hemiparesis and forced eye and head deviations. All patients had suffered large MCA-territory stroke. Twenty patients had complete MCA-territory stroke; 5 patients had additional anterior or posterior artery territory infarctions. The cause of stroke was cardioembolism in 18 patients, internal carotid artery dissection with secondary MCA embolization in 3 patients, atherothrombotic disease at the carotid bifurcation in 1 patient, and unknown in 3 patients. Of 25 patients, 11 (44%) who underwent moderate hypothermic therapy for major space-occupying infarction died (Table 1).

View this table: [in this window] [in a new window]   Table 1. Patient Characteristics

Mean interval between onset of symptoms of ischemic stroke and initiation of hypothermia was 14 hours (range, 4 to 24 hours). Time required for cooling to 33°C bladder temperature was from 3.5 to 6.2 hours. Moderate hypothermia was sustained for 48 to 72 hours (median, 65 hours). Passive rewarming took between 17 and 24 hours (median, 18 hours). The monitoring device was inserted at a mean of 10 hours after stroke onset (range, 6 to 32 hours), and the average ICP monitoring period varied between 3 and 7 days (mean, 4.9±2.5 days). Mean initial ICP was 20.9±12.4 mm Hg (range, 13 to 36 mm Hg). In all patients, ICP values decreased with initiation of moderate hypothermia to mean values of 14.5±4.2 mm Hg. When the steady state of hypothermia was reached, ICP values were 13.4±8.3 mm Hg, which was significantly lower than initial values (P<0.05). During rewarming, ICP values rose continuously; the highest measured mean values were 19.4±8.7 mm Hg (range, 17 to 52 mm Hg). In the group of patients who died, mean ICP values were 22±12.6 mm Hg (range, 20.4 to 52 mm Hg). Mean initial CPP was 68 mm Hg (range, 60 to 85 mm Hg). After induction of moderate hypothermia, mean CPP was 78 mm Hg (range, 65 to 90 mm Hg) (P<0.05). After rewarming, CPP varied between 60 and 90 mm Hg (mean, 70 mm Hg). Eighteen patients received vasopressors to maintain CPP values >70 mm Hg after rewarming (Table 2).

View this table: [in this window] [in a new window]   Table 2. Effects of Moderate Hypothermia on Intracranial and Systemic Physiological Characteristics

In all patients, intraparenchymatous brain temperature before initiation of hypothermia exceeded body-core temperature, with a mean of 1.5±0.3°C (range, 1.0°C to 2.1°C). The difference between brain and body-core temperatures varied individually and over the measurement period. Hence, the difference between brain and body-core temperatures was independent of ICP or CPP. With induction of moderate hypothermia, the temperature gradient between body core and brain decreased by a mean of 0.3±0.4°C (range, -0.3°C to 1.0°C).

All 14 patients who survived their severe strokes were discharged to rehabilitation programs. Their neurological outcome according to the SSS score 4 weeks after stroke was 29 (range, 25 to 37). Three months after stroke, SSS was 38 (range, 28 to 48); w 1 patient died of a pulmonary embolus. The median BI of the surviving patients was 70 (range, 60 to 85), and the mean Rankin scale was 2.6 (range, 2 to 4).

Side Effects
Before initiation of hypothermia, a systemic response to infection was absent in all 25 patients, whereas after rewarming, 7 patients had a septic syndrome according to the above-mentioned criteria. The most frequent complication of moderate hypothermia was pneumonia, which was encountered in 10 of the 25 patients (40%). In 6 patients, pneumonia was diagnosed during rewarming. Activated prothrombin and partial thromboplastin times remained unchanged during hypothermia. However, platelet count decreased significantly during hypothermia and was lower than initial values. This effect lasted up to 3 days after rewarming. The observed thrombopenia was asymptomatic and did not cause any bleeding complications. Urine output and creatinine clearance did not demonstrate a statistically significant difference before, during, or after induction of hypothermia. A significant increase in serum amylase and lipase in 7 of the 25 patients (28%) with maximal lipase levels of 1200 U/L (normal value, <150 U/L) occurred under hypothermic therapy. However, there were no clinical signs and symptoms of acute pancreatitis in any patient. Analysis of serum sodium concentrations remained unchanged during hypothermia, but serum potassium concentrations were markedly decreased during cooling and in the steady state of hypothermia. Cardiac arrhythmias (with prolongation of the PR and QT intervals) and sinus bradycardia were seen in 15 patients, whereas no patient developed severe hypotension or required further antiarrhythmic therapy (Table 3).

View this table: [in this window] [in a new window]   Table 3. Side Effects of Moderate Hypothermia on Various Organ Systems

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Conventional treatment of elevated ICP after ischemic stroke consists of artificial ventilation, osmotherapy, and barbiturate administration. The value and duration of these measures have come under scrutiny. Prolonged hyperventilation has been discouraged because the potential decrease in cerebral arterial blood flow resulting from additional hypocarbia might exacerbate tissue ischemia.²⁵ Early use of such agents as glycerol or mannitol may, at least in theory, actually hasten tissue shifts and therefore lead to an aggravation of brain edema.²⁶ Barbiturate therapy has as yet failed to be of therapeutic benefit in the treatment of postischemic brain edema.²⁷ Because of the potential adverse effects of "conventional therapy," new therapeutic concepts for the treatment of brain edema have to be used.

In animal models with both focal and global ischemia, moderate hypothermia reduced secondary brain injury and infarction size and improved neurological outcome.^{2 3 4 5 6} However, most of these studies used a narrow time window, with hypothermia initiated within 60 to 90 minutes after induction of experimental ischemia. Markarian et al²⁸ demonstrated the best results in a focal ischemia model when hypothermia was applied within the first 30 minutes and lasted 3 hours. Applying these data to clinical practice would suggest that induced hypothermia is beneficial only in the very first few hours after stroke onset.

Several neurosurgical studies showed a positive effect of mild hypothermia on uncontrollable intracranial hypertension after severe head trauma.^{13 14 15 16} Head-injured patients treated with mild hypothermia between 32°C and 34°C core temperature had a significant reduction in ICP and cerebral blood flow compared with the normothermia-treated control group. All studies indicated better outcome with hypothermia and a beneficial effect in limiting secondary brain injury. In most of these studies, hypothermia was delivered within the first 6 to 16 hours after head injury. Duration of hypothermia varied from 24 to 48 hours, whereas neither the optimal duration of hypothermia nor the optimal time after the trauma for therapy in these patients could be identified.

Similar to these clinical studies, hypothermia was induced in this study a mean of 14 hours after the ischemic injury. Obviously, this time delay has to be reduced in further trials because according to experimental data, hypothermia has the most positive effect when applied very early after cerebral ischemia. We chose a relatively long duration of hypothermia to overcome maximum brain swelling, which is known to occur between days 2 and 5 after ischemia.^{29 30 31 32}

In space-occupying MCA infarction, outcome is fatal in most patients, with a mortality rate of about 80% with standard treatment.^{31 32} Clinically, the patients have a severe hemispheric syndrome with head turning and eye deviation. They usually show a rapid decline in consciousness and develop the signs of herniation 2 to 4 days after onset of symptoms.^{31 32} All patients in this study fulfilled the criteria for diagnosis of a "malignant" MCA infarction.³¹ However, the mortality rate was only 44%, and survivors reached a favorable outcome with a mean BI of 70 (Figure 1 and Table 4).

View larger version (12K): [in this window] [in a new window]   Figure 1. Survival curve of all patients treated with moderate hypothermia compared with patients treated with conventional therapy.31

View this table: [in this window] [in a new window]   Table 4. Comparison Between Patients Treated With Hypothermia and Natural History Data

It is known from animal models with global ischemia and traumatic brain injury that moderate hypothermia attenuates secondary brain damage by reducing cerebral ischemia and postischemic brain edema and preserving the blood-brain barrier. Hypothermia significantly reduced the ICP, which is similar to the results of Marion et al¹⁴ and Shiozaki et al,¹⁶ who used hypothermic therapy in traumatic brain injuries. With a merely unaffected mean arterial blood pressure and increased CPP, hypothermic therapy appears to benefit stroke patients because uncontrolled intracranial hypertension is the main cause of death in the first week after stroke.^{29 30 31 32} However, rewarming the patients constantly led to a secondary increase in ICP, which required additional ICP therapy with mannitol. In some cases, it even exaggerated initial ICP levels. It is known that the rewarming period is a high-risk time for brain injury because metabolic needs may outstrip oxygen delivery at various temperatures.³³ Of the 11 patients who died, 5 had untreatable elevation of ICP during rewarming, whereas in 6 patients, signs of transtentorial herniation occurred with a body temperature of 33°C. The rebound increase in ICP after rewarming might suggest that hypothermia only delays the deleterious effects caused by ischemic injury and thus does not result in any substantial improvement. The fact that most patients had lower ICP levels than before induction of hypothermia speaks clearly against this hypothesis (Figure 2). However, rewarming has to be considered the "critical phase" of hypothermic therapy. This rebound after rewarming might be due to a proposed hypermetabolic response after induced hypothermia, as it was described after cardiopulmonary bypass surgery.³⁴

View larger version (32K): [in this window] [in a new window]   Figure 2. Time course of daily maximum ICP values in those patients treated with hypothermia who survived and those who subsequently died. *P<0.05.

The brain temperatures of all 25 patients were consistently higher than body-core temperatures, confirming previous data that showed a significant gradient between body-core and brain temperatures in neurotrauma patients.^{35 36} This may be explained by the high metabolic activity of cerebral tissue with considerable production of heat.³⁷ Another possibility is that in the early stages of infarct formation, a decrease in cerebral blood flow may result in a decreased capacity for the blood to carry off heat generated by local cerebral metabolism.

In animal studies, it was reported that toxicity from moderate hypothermia increases as the temperature is further decreased and as the duration of hypothermia is increased.^{38 39} In this study, we could not observe a significant increase in the occurrence of side effects between patients cooled for 48 hours and those treated for 72 hours. Hypothermia affects virtually every organ system. The extent of hypothermia is limited by ventricular ectopy and fibrillation, but this is known to occur only at temperatures <30°C.¹ In the present study, pneumonia was the only severe side effect of moderate, induced hypothermia. However, impairment of pulmonary gas exchange, caused by atelectasis, is a common problem in patients who are ventilated longer. The reported incidence of pneumonia in these patients ranges from 10% to 40%.⁴⁰ The risk of developing pneumonia increases when coma, trauma, or impaired airway reflexes are present at admission to the critical care unit.⁴⁰ In our study, the incidence of pneumonia of 40% is comparable to these reported data and similar to the findings of Metz and colleagues,¹⁵ who observed pneumonia in 50% of their hypothermically treated patients within the first week in the intensive care unit. Other side effects of hypothermia shown in animal studies are clotting abnormalities and coagulopathy.^{41 42} In baboons, systemic hypothermia led to increased bleeding times.⁴³ In humans, the enzymatic reactions of the coagulation cascade were shown to be strongly inhibited by hypothermia.^{44 45} However, we could not observe any severe clotting abnormalities in the hypothermia-treated patients. On the other hand, a decrease in platelet counts during the cooling period was regularly seen, with recovery only after rewarming. Also pancreatitis with high serum amylase and lipase levels was observed after hypothermic therapy. The association between hypothermia and pancreatitis is poorly understood yet.⁴⁶ In our study, the pathological signs of pancreatitis with elevated levels of amylase and lipase were completely reversible after rewarming.

In conclusion, induced, moderate hypothermia can decrease ICP and may improve mortality in patients with severe postischemic brain edema. Important side effects are reduction in platelet count, increased rate of pneumonia, and elevation of serum amylase and lipase levels. Our own preliminary results suggest a beneficial effect of moderate hypothermia in the treatment of severe space-occupying MCA infarction. However, our data call for a randomized trial of hypothermia in the therapy of malignant MCA infarction. Whether early hypothermic therapy within the first 6 hours after onset of symptoms can reduce infarct size has to be clarified in further clinical trials.

	Acknowledgments

 
This work was supported by a grant from the German Research Foundation (Ku 294/18-4) to Dr Schwab. Dr Keller was supported by a grant from the Swiss National Science Foundation. We thank all our fellow workers, residents, nursing team, and neurophysiology technicians at the Neurocritical Care Unit, University of Heidelberg, for their continuous support of this study.

Received May 26, 1998; revision received July 31, 1998; accepted September 22, 1998.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 
1. Safar P, Klain M, Tisherman S. Selective brain cooling after cardiac arrest. Crit Care Med. 1996;24:911–914.[Medline] [Order article via Infotrieve]

2. Busto R, Dietrich WD, Globus MY-T, Ginsberg MD. Postischemic moderate hypothermia inhibits CA1 hippocampal ischemic neuronal injury. Neurosci Lett. 1989;101:299–304.[Medline] [Order article via Infotrieve]

3. Coimbra C, Wieloch T. Moderate hypothermia mitigates neuronal damage in the rat brain when initiated several hours following transient cerebral ischemia. Acta Neuropathol. 1994;87:325–331.[Medline] [Order article via Infotrieve]

4. Karibe H, Chen J, Zarow GJ, Graham SH, Weinstein PR. Delayed induction of mild hypothermia to reduce infarct volume after temporary middle cerebral artery occlusion in rats. J Neurosurg. 1994;80:112–119.[Medline] [Order article via Infotrieve]

5. Morikawa E, Ginsberg MD, Dietrich WD, Duncan RC, Kraydieh S, Globus MY-T, Busto R. The significance of brain temperature in focal cerebral ischemia: histopathological consequences of middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab. 1992;12:380–389.[Medline] [Order article via Infotrieve]

6. Xue D, Huang ZG, Smith KE, Buchan AM. Immediate or delayed mild hypothermia prevents focal cerebral infarction. Brain Res. 1992;587:66–72.[Medline] [Order article via Infotrieve]

7. Busto R, Dietrich WD, Globus MY-T, Valdés I, Scheinberg P, Ginsberg MD. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab. 1987;7:729–738.[Medline] [Order article via Infotrieve]

8. Chopp M, Welch KMA, Tidwell CD, Knight R, Helpern JA. Effect of mild hyperthermia on recovery of metabolic function after global cerebral ischemia in cats. Stroke. 1988;19:1521–1525.[Abstract/Free Full Text]

9. Dietrich WD, Alonso O, Halley M, Busto R. Delayed posttraumatic brain hyperthermia worsens outcome after fluid percussion brain injury: a light and electron microscopic study in rats. Neurosurgery. 1996;38:533–541.[Medline] [Order article via Infotrieve]

10. Ginsberg MD, Sternau LL Globus MYT, Dietrich WD, Busto R. Therapeutic modulation of brain temperature: relevance to ischemic brain injury. Cerebrovasc Brain Metab Rev. 1992;4:189–225.[Medline] [Order article via Infotrieve]

11. Maher J, Hachinski V. Hypothermia as a potential treatment for cerebral ischemia. Cerebrovasc Brain Metab Rev. 1993;5:277–300.[Medline] [Order article via Infotrieve]

12. Nakashima K, Todd MM. Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization. Stroke. 1996;27:913–918.[Abstract/Free Full Text]

13. Clifton GL, Allen S, Barrodale P, Plenger P, Berry J, Koch S, Fletcher J, Hayes R, Choi SC. A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma. 1993;10:263–271.[Medline] [Order article via Infotrieve]

14. Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM, Palmer AM, Wisniewski SR, DeKosky ST. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med. 1997;336:540–546.[Abstract/Free Full Text]

15. Metz C, Holzschuh M, Bein T, Woertgen C, Frey A, Frey I, Taeger K, Brawanski A. Moderate hypothermia in patients with severe head injury: cerebral and extracerebral effects. J Neurosurg. 1996;85:533–541.[Medline] [Order article via Infotrieve]

16. Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A, Yoshioka T, Sugimoto T. Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg. 1993;79:363–368.[Medline] [Order article via Infotrieve]

17. Azzimondi G, Bassein L, Nonino F, Fiorani L, Vignatelli L, Re G, D'Alessandro R. Fever in acute stroke worsens prognosis. Stroke. 1995;26:2040–2043.[Abstract/Free Full Text]

18. Reith J, Jorgensen S, Pedersen PM, Nakayama H, Raaschou HO, Jeppesen LL, Olsen TS. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet. 1996;347:422–425.[Medline] [Order article via Infotrieve]

19. Scandinavian Stroke Study Group. Multicenter trial of hemodilution in ischemic stroke: background and study protocol. Stroke. 1985;16:885–890.[Free Full Text]

20. Teasdale G, Jannett B. Assessment of outcome after severe brain damage. Lancet. 1975;1:480–484.[Medline] [Order article via Infotrieve]

21. Rankin J. Cerebral vascular accidents in people over the age of 60: prognosis. Scott Med J. 1957;2:200–215.[Medline] [Order article via Infotrieve]

22. Mahoney F, Barthel D. Functional evaluation: the Barthel index. Md Med J. 1965;14:61–65.

23. Verhaegen MJJ, Todd MM, Hindman BJ, Warner DS. Cerebral autoregulation during moderate hypothermia in rats. Stroke. 1993;24:407–414.[Abstract/Free Full Text]

24. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864–874.[Medline] [Order article via Infotrieve]

25. Muizelaar JP, Marmarou A, Ward JD, Kontos HA, Choi SC; Becker DP, Gruemer H, Young HF. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg. 1991;75:731–739.[Medline] [Order article via Infotrieve]

26. Kaufmann AM, Cardoso ER. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg. 1992;77:584–589.[Medline] [Order article via Infotrieve]

27. Schwab S, Spranger M, Schwarz S, Hacke W. Barbiturate coma in severe hemispheric stroke: useful or obsolete? Neurology. 1997;48:1608–1613.[Abstract/Free Full Text]

28. Markarian GZ, Lee JH, Stein DJ, Hong SC. Mild hypothermia: therapeutic window after experimental cerebral ischemia. Neurosurgery. 1996;38:542–551.[Medline] [Order article via Infotrieve]

29. Ng LKY, Nimmannitya J. Massive cerebral infarction with severe brain swelling: a clinicopathological study. Stroke. 1970;1:158–163.[Abstract/Free Full Text]

30. Bounds JV, Wiebers DO, Whisnant JP, Okazaki H. Mechanisms and timing of deaths from cerebral infarction. Stroke. 1981;12:474–477.[Abstract/Free Full Text]

31. Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, van Kummer R. Malignant middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol. 1996;53:309–315.[Abstract/Free Full Text]

32. Ropper AH, Shafran B. Brain edema after stroke: clinical syndrome and intracranial pressure. Arch Neurol. 1984;41:26–29.[Abstract/Free Full Text]

33. Ausman JI, McCormick PW, Stewart M, Lewis G, Dujovny M, Balakrishnan G, Malik GM, Ghaly RF. Cerebral oxygen metabolism during hypothermic circulatory arrest in humans. J Neurosurg. 1993;79:810–815.[Medline] [Order article via Infotrieve]

34. Chiara O, Giomarelli P, Biagioli B, Rosi R, Gattinoni L. Hypermetabolic response after hypothermic cardiopulmonary bypass. Crit Care Med. 1987;15:995–999.[Medline] [Order article via Infotrieve]

35. Mellergård P, Nordstroem C-H. Intracerebral temperature in neurosurgical patients. Neurosurgery. 1991;28:709–713.[Medline] [Order article via Infotrieve]

36. Schwab S, Spranger M, Aschoff A, Steiner T, Hacke W. Brain temperature monitoring and modulation in patients with severe MCA infarction. Neurology. 1997;48:762–767.[Abstract/Free Full Text]

37. Hayward JN, Baker MA. Role of cerebral arterial blood in the regulation of brain temperature in the monkey. Am J Physiol. 1968;215:389–403.

38. Steen PA, Soule EH, Michenfelder JD. Detrimental effects of prolonged hypothermia in cats and monkeys with and without regional cerebral ischemia. Stroke. 1979;10:522–529.[Abstract/Free Full Text]

39. Michenfelder JD, Milde JH. Failure of prolonged hypocapnia, hypothermia, or hypertension to favorably alter acute stroke in primates. Stroke. 1977;8:87–91.[Abstract/Free Full Text]

40. Chevret S, Hemmer M, Carlet J, Langer M. Incidence and risk factors of pneumonia acquired in intensive care units: results from a multicenter prospective study on 996 patients. Int Care Med. 1993;19:256–264.[Medline] [Order article via Infotrieve]

41. Clifton GL, Jiang JY, Lyeth BG, Jenkins LW, Hamm RJ, Hayes RL. Marked protection by moderate hypothermia after experimental traumatic brain injury. J Cereb Blood Flow Metab. 1991;11:114–121.[Medline] [Order article via Infotrieve]

42. Reed RL, Johnston TD, Hudson JD, Fischer RP. The disparity between hypothermic coagulopathy and clotting studies. J Trauma. 1992;33:465–470.[Medline] [Order article via Infotrieve]

43. Valeri CR, Cassidy G, Khuri S, Feingold H, Rango G, Atschule MD. Hypothermia induced reversible platelet dysfunction. Ann Surg. 1987;205:175–181.[Medline] [Order article via Infotrieve]

44. Resnick DK, Marion DW, Darby JM. The effect of hypothermia on the incidence of delayed traumatic intracerebral hemorrhage. Neurosurgery. 1994;34:252–256.[Medline] [Order article via Infotrieve]

45. Rohrer MJ, Natale AM. Effect of hypothermia on the coagulation cascade. Crit Care Med. 1992;20:1402–1405.[Medline] [Order article via Infotrieve]

46. Foulis AK. Morphological study of the relation between accidental hypothermia and acute pancreatitis. J Clin Pathol. 1982;35:1244–1248.[Abstract/Free Full Text]

This article has been cited by other articles:

				B. P. Meloni, F. L. Mastaglia, and N. W. Knuckey Review: Therapeutic applications of hypothermia in cerebral ischaemia Therapeutic Advances in Neurological Disorders, September 1, 2008; 1(2): 75 - 98. [Abstract] [PDF]

				J. Varon and P. Acosta Therapeutic Hypothermia: Past, Present, and Future Chest, May 1, 2008; 133(5): 1267 - 1274. [Abstract] [Full Text] [PDF]

				J. Bardutzky and S. Schwab Antiedema Therapy in Ischemic Stroke Stroke, November 1, 2007; 38(11): 3084 - 3094. [Abstract] [Full Text] [PDF]

				R. Kollmar and S. Schwab Ischaemic stroke: acute management, intensive care, and future perspectives Br. J. Anaesth., July 1, 2007; 99(1): 95 - 101. [Abstract] [Full Text] [PDF]

				H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation, May 22, 2007; 115(20): e478 - e534. [Abstract] [Full Text] [PDF]

				H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists Stroke, May 1, 2007; 38(5): 1655 - 1711. [Abstract] [Full Text] [PDF]

				I. Dorotta, P. Kimball-Jones, and R. Applegate II Deep hypothermia and circulatory arrest in adults. Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2007; 11(1): 66 - 76. [Abstract] [PDF]

				C. M. Gebauer, M. Knuepfer, E. Robel-Tillig, F. Pulzer, and C. Vogtmann Hemodynamics Among Neonates With Hypoxic-Ischemic Encephalopathy During Whole-Body Hypothermia and Passive Rewarming Pediatrics, March 1, 2006; 117(3): 843 - 850. [Abstract] [Full Text] [PDF]

				A D Edwards and D V Azzopardi Therapeutic hypothermia following perinatal asphyxia. Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2006; 91(2): F127 - F131. [Abstract] [Full Text] [PDF]

				Part 9: Adult Stroke Circulation, December 13, 2005; 112(24_suppl): IV-111 - IV-120. [Full Text] [PDF]

				Part 9: Stroke Circulation, November 29, 2005; 112(22_suppl): III-110 - III-104. [Full Text] [PDF]

				K. A. Boddicker, Y. Zhang, M. B. Zimmerman, L. R. Davies, and R. E. Kerber Hypothermia Improves Defibrillation Success and Resuscitation Outcomes From Ventricular Fibrillation Circulation, June 21, 2005; 111(24): 3195 - 3201. [Abstract] [Full Text] [PDF]

				C. Berger, P. Schramm, and S. Schwab Reduction of Diffusion-Weighted MRI Lesion Volume After Early Moderate Hypothermia in Ischemic Stroke Stroke, June 1, 2005; 36(6): e56 - e58. [Abstract] [Full Text] [PDF]

				D. W. Krieger and M. A. Yenari Therapeutic Hypothermia for Acute Ischemic Stroke: What Do Laboratory Studies Teach Us? Stroke, June 1, 2004; 35(6): 1482 - 1489. [Abstract] [Full Text] [PDF]

				S. J. Lee, K. H. Lee, D. G. Na, H. S. Byun, Y. B. Kim, Y.-M. Shon, S.-J. Cho, J. Lee, C.-S. Chung, and S.-C. Hong Multiphasic Helical Computed Tomography Predicts Subsequent Development of Severe Brain Edema in Acute Ischemic Stroke Arch Neurol, April 1, 2004; 61(4): 505 - 509. [Abstract] [Full Text] [PDF]

				G. H. Danton and W. D. Dietrich The Search for Neuroprotective Strategies in Stroke AJNR Am. J. Neuroradiol., February 1, 2004; 25(2): 181 - 194. [Full Text] [PDF]

				C. Berger and S. Schwab Editorial Comment--"Malignant" or Not: Is There a Role for In Vivo Neurochemistry? Stroke, December 1, 2003; 34(12): 2914 - 2915. [Full Text] [PDF]

				C. Dohmen, B. Bosche, R. Graf, F. Staub, L. Kracht, J. Sobesky, M. Neveling, G. Brinker, and W.-D. Heiss Prediction of Malignant Course in MCA Infarction by PET and Microdialysis Stroke, September 1, 2003; 34(9): 2152 - 2158. [Abstract] [Full Text] [PDF]

				S. Zausinger, K. Scholler, N. Plesnila, and R. Schmid-Elsaesser Combination Drug Therapy and Mild Hypothermia After Transient Focal Cerebral Ischemia in Rats Stroke, September 1, 2003; 34(9): 2246 - 2251. [Abstract] [Full Text] [PDF]

				S. Horstmann, P. Kalb, J. Koziol, H. Gardner, and S. Wagner Profiles of Matrix Metalloproteinases, Their Inhibitors, and Laminin in Stroke Patients: Influence of Different Therapies Stroke, September 1, 2003; 34(9): 2165 - 2170. [Abstract] [Full Text] [PDF]

				S. Schwab and W. Hacke Surgical Decompression of Patients With Large Middle Cerebral Artery Infarcts Is Effective Stroke, September 1, 2003; 34(9): 2304 - 2305. [Full Text] [PDF]

				W. J. Mack, J. Huang, C. Winfree, G. Kim, M. Oppermann, J. Dobak, B. Inderbitzen, S. Yon, S. Popilskis, J. Lasheras, et al. Ultrarapid, Convection-Enhanced Intravascular Hypothermia: A Feasibility Study in Nonhuman Primate Stroke Stroke, August 1, 2003; 34(8): 1994 - 1999. [Abstract] [Full Text] [PDF]

				A. G. Doufas, A. Wadhwa, C.-M. Lin, Y. M. Shah, K. Hanni, and D. I. Sessler Neither Arm nor Face Warming Reduces the Shivering Threshold in Unanesthetized Humans Stroke, July 1, 2003; 34(7): 1736 - 1740. [Abstract] [Full Text] [PDF]

				L. A. McIntyre, D. A. Fergusson, P. C. Hebert, D. Moher, and J. S. Hutchison Prolonged Therapeutic Hypothermia After Traumatic Brain Injury in Adults: A Systematic Review JAMA, June 11, 2003; 289(22): 2992 - 2999. [Abstract] [Full Text] [PDF]

				S Schwarz, S Schwab, K Klinga, C Maser-Gluth, and M Bettendorf Neuroendocrine changes in patients with acute space occupying ischaemic stroke J. Neurol. Neurosurg. Psychiatry, June 1, 2003; 74(6): 725 - 727. [Abstract] [Full Text] [PDF]

				M. Pokela, J. Heikkinen, F. Biancari, E. Ronka, T. Kaakinen, V. Vainionpaa, K. T. Kiviluoma, P. Romsi, E. Leo, J. Hirvonen, et al. Topical head cooling during rewarming after experimental hypothermic circulatory arrest Ann. Thorac. Surg., June 1, 2003; 75(6): 1899 - 1910. [Abstract] [Full Text] [PDF]

				A. G. Doufas, C.-M. Lin, M.-I. Suleman, E. B. Liem, R. Lenhardt, N. Morioka, O. Akca, Y. M. Shah, A. R. Bjorksten, and D. I. Sessler Dexmedetomidine and Meperidine Additively Reduce the Shivering Threshold in Humans Stroke, May 1, 2003; 34(5): 1218 - 1223. [Abstract] [Full Text] [PDF]

				H. P. Adams Jr, R. J. Adams, T. Brott, G. J. del Zoppo, A. Furlan, L. B. Goldstein, R. L. Grubb, R. Higashida, C. Kidwell, T. G. Kwiatkowski, et al. Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association Stroke, April 1, 2003; 34(4): 1056 - 1083. [Full Text] [PDF]

				W. D. Dietrich and J. W. Kuluz New Research in the Field of Stroke: Therapeutic Hypothermia after Cardiac Arrest Stroke, April 1, 2003; 34(4): 1051 - 1053. [Full Text] [PDF]

				M. W. Dae, D. W. Gao, P. C. Ursell, C. A. Stillson, and D. I. Sessler Safety and Efficacy of Endovascular Cooling and Rewarming for Induction and Reversal of Hypothermia in Human-Sized Pigs Stroke, March 1, 2003; 34(3): 734 - 738. [Abstract] [Full Text] [PDF]

				P. D. Schellinger, J. B. Fiebach, W. Hacke, and J. Rother Imaging-Based Decision Making in Thrombolytic Therapy for Ischemic Stroke: Present Status Stroke, February 1, 2003; 34(2): 575 - 583. [Abstract] [Full Text] [PDF]

				S. R. Dixon, R. J. Whitbourn, M. W. Dae, E. Grube, W. Sherman, G. L. Schaer, J. S. Jenkins, D. S. Baim, R. J. Gibbons, R. E. Kuntz, et al. Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction J. Am. Coll. Cardiol., December 4, 2002; 40(11): 1928 - 1934. [Abstract] [Full Text] [PDF]

				A. G. Doufas, O. Akca, A. Barry, D. A. Petrusca, M.-I. Suleman, N. Morioka, J. J. Guarnaschelli, and D. I. Sessler Initial Experience with a Novel Heat-Exchanging Catheter in Neurosurgical Patients Anesth. Analg., December 1, 2002; 95(6): 1752 - 1756. [Abstract] [Full Text] [PDF]

				D. Georgiadis, S. Schwarz, D.H. Evans, S. Schwab, and R.W. Baumgartner Cerebral Autoregulation Under Moderate Hypothermia in Patients With Acute Stroke Stroke, December 1, 2002; 33(12): 3026 - 3029. [Abstract] [Full Text] [PDF]

				J. P. Broderick and W. Hacke Treatment of Acute Ischemic Stroke: Part II: Neuroprotection and Medical Management Circulation, September 24, 2002; 106(13): 1736 - 1740. [Full Text] [PDF]

				J. F. Arenillas, A. Rovira, C. A. Molina, E. Grive, J. Montaner, J. Alvarez-Sabin, and K.-O. Lovblad Prediction of Early Neurological Deterioration Using Diffusion- and Perfusion-Weighted Imaging in Hyperacute Middle Cerebral Artery Ischemic Stroke * Editorial Comment Stroke, September 1, 2002; 33(9): 2197 - 2205. [Abstract] [Full Text] [PDF]

				W.-R. Schabitz, A. Giuffrida, C. Berger, A. Aschoff, M. Schwaninger, S. Schwab, and D. Piomelli Release of Fatty Acid Amides in a Patient With Hemispheric Stroke: A Microdialysis Study Stroke, August 1, 2002; 33(8): 2112 - 2114. [Abstract] [Full Text] [PDF]

				L.P. Kammersgaard, H.S. Jorgensen, J.A. Rungby, J. Reith, H. Nakayama, U.J. Weber, J. Houth, and T.S. Olsen Admission Body Temperature Predicts Long-Term Mortality After Acute Stroke: The Copenhagen Stroke Study Stroke, July 1, 2002; 33(7): 1759 - 1762. [Abstract] [Full Text] [PDF]

				R. Kollmar, W.R. Schabitz, S. Heiland, D. Georgiadis, P.D. Schellinger, J. Bardutzky, and S. Schwab Neuroprotective Effect of Delayed Moderate Hypothermia After Focal Cerebral Ischemia: An MRI Study Stroke, July 1, 2002; 33(7): 1899 - 1904. [Abstract] [Full Text] [PDF]

				D. Georgiadis, S. Schwarz, A. Aschoff, and S. Schwab Hemicraniectomy and Moderate Hypothermia in Patients With Severe Ischemic Stroke Stroke, June 1, 2002; 33(6): 1584 - 1588. [Abstract] [Full Text] [PDF]

				M. S. Wainwright, H. Sheng, Y. Sato, G. Burkhard Mackensen, R. P. Steffen, R. D. Pearlstein, and D. S. Warner Pharmacological correction of hypothermic P50 shift does not alter outcome from focal cerebral ischemia in rats Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1863 - H1870. [Abstract] [Full Text] [PDF]

				P. Romsi, J. Heikkinen, F. Biancari, M. Pokela, J. Rimpilainen, V. Vainionpaa, J. Hirvonen, V. Jantti, K. Kiviluoma, V. Anttila, et al. Prolonged mild hypothermia after experimental hypothermic circulatory arrest in a chronic porcine model J. Thorac. Cardiovasc. Surg., April 1, 2002; 123(4): 724 - 734. [Abstract] [Full Text] [PDF]

				S. Schwarz, D. Georgiadis, A. Aschoff, and S. Schwab Effects of Induced Hypertension on Intracranial Pressure and Flow Velocities of the Middle Cerebral Arteries in Patients With Large Hemispheric Stroke Stroke, April 1, 2002; 33(4): 998 - 1004. [Abstract] [Full Text] [PDF]

				S. A. Bernard, T. W. Gray, M. D. Buist, B. M. Jones, W. Silvester, G. Gutteridge, and K. Smith Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia N. Engl. J. Med., February 21, 2002; 346(8): 557 - 563. [Abstract] [Full Text] [PDF]

				S. Schwarz, D. Georgiadis, A. Aschoff, and S. Schwab Effects of Body Position on Intracranial Pressure and Cerebral Perfusion in Patients With Large Hemispheric Stroke Stroke, February 1, 2002; 33(2): 497 - 501. [Abstract] [Full Text] [PDF]

				C. Berger, W.-R. Schabitz, D. Georgiadis, T. Steiner, A. Aschoff, and S. Schwab Effects of Hypothermia on Excitatory Amino Acids and Metabolism in Stroke Patients: A Microdialysis Study Stroke, February 1, 2002; 33(2): 519 - 524. [Abstract] [Full Text] [PDF]

				S. E. Kasner, T. Wein, P. Piriyawat, C. E. Villar-Cordova, J. A. Chalela, D. W. Krieger, L. B. Morgenstern, S. E. Kimmel, J. C. Grotta, and H.-C. Koennecke Acetaminophen for Altering Body Temperature in Acute Stroke: A Randomized Clinical Trial * Editorial Comment: A Randomized Clinical Trial Stroke, January 1, 2002; 33(1): 130 - 135. [Abstract] [Full Text] [PDF]

				S. Schwarz, D. Georgiadis, A. Aschoff, and S. Schwab Effects of Hypertonic (10%) Saline in Patients With Raised Intracranial Pressure After Stroke Stroke, January 1, 2002; 33(1): 136 - 140. [Abstract] [Full Text] [PDF]

				H.-C. Koennecke and S. Leistner Prophylactic antipyretic treatment with acetaminophen in acute ischemic stroke:: A pilot study Neurology, December 26, 2001; 57(12): 2301 - 2303. [Abstract] [Full Text] [PDF]

				T. Steiner, T. Friede, A. Aschoff, P. D. Schellinger, S. Schwab, and W. Hacke Effect and Feasibility of Controlled Rewarming After Moderate Hypothermia in Stroke Patients With Malignant Infarction of the Middle Cerebral Artery Stroke, December 1, 2001; 32(12): 2833 - 2835. [Abstract] [Full Text] [PDF]

				T. Steiner, J. Pilz, P. Schellinger, R. Wirtz, V. Friederichs, A. Aschoff, and W. Hacke Multimodal Online Monitoring in Middle Cerebral Artery Territory Stroke Stroke, November 1, 2001; 32(11): 2500 - 2506. [Abstract] [Full Text] [PDF]

				D. Georgiadis, S. Schwarz, R. Kollmar, and S. Schwab Endovascular Cooling for Moderate Hypothermia in Patients With Acute Stroke: First Results of a Novel Approach Stroke, November 1, 2001; 32(11): 2550 - 2553. [Abstract] [Full Text] [PDF]

				A. Doerfler, S. Schwab, T. T. Hoffmann, T. Engelhorn, and M. Forsting Combination of Decompressive Craniectomy and Mild Hypothermia Ameliorates Infarction Volume After Permanent Focal Ischemia in Rats Stroke, November 1, 2001; 32(11): 2675 - 2681. [Abstract] [Full Text] [PDF]

				M. Mokhtarani, A. N. Mahgoub, N. Morioka, A. G. Doufas, M. Dae, T. E. Shaughnessy, A. R. Bjorksten, and D. I. Sessler Buspirone and Meperidine Synergistically Reduce the Shivering Threshold Anesth. Analg., November 1, 2001; 93(5): 1233 - 1239. [Abstract] [Full Text] [PDF]

				S. Schwab, D. Georgiadis, J. Berrouschot, P. D. Schellinger, C. Graffagnino, and S. A. Mayer Feasibility and Safety of Moderate Hypothermia After Massive Hemispheric Infarction Stroke, September 1, 2001; 32(9): 2033 - 2035. [Abstract] [Full Text] [PDF]

				D. Georgiadis, S. Schwarz, R. W. Baumgartner, R. Veltkamp, and S. Schwab Influence of Positive End-Expiratory Pressure on Intracranial Pressure and Cerebral Perfusion Pressure in Patients With Acute Stroke Stroke, September 1, 2001; 32(9): 2088 - 2092. [Abstract] [Full Text] [PDF]

				S. E. Kasner, A. M. Demchuk, J. Berrouschot, E. Schmutzhard, L. Harms, P. Verro, J. A. Chalela, R. Abbur, H. McGrade, I. Christou, et al. Predictors of Fatal Brain Edema in Massive Hemispheric Ischemic Stroke Stroke, September 1, 2001; 32(9): 2117 - 2123. [Abstract] [Full Text] [PDF]

				T. Steiner, P. Ringleb, and W. Hacke Treatment options for large hemispheric stroke Neurology, September 1, 2001; 57(90002): S61 - 68. [Abstract] [Full Text]

				D. W. Krieger, M. A. De Georgia, A. Abou-Chebl, J. C. Andrefsky, C. A. Sila, I. L. Katzan, M. R. Mayberg, and A. J. Furlan Cooling for Acute Ischemic Brain Damage (COOL AID): An Open Pilot Study of Induced Hypothermia in Acute Ischemic Stroke Stroke, August 1, 2001; 32(8): 1847 - 1854. [Abstract] [Full Text] [PDF]

				S. Schneweis, M. Grond, F. Staub, G. Brinker, M. Neveling, C. Dohmen, R. Graf, W.-D. Heiss, and A. Shuaib Predictive Value of Neurochemical Monitoring in Large Middle Cerebral Artery Infarction Editorial Comment Stroke, August 1, 2001; 32(8): 1863 - 1867. [Abstract] [Full Text] [PDF]

				D. W.J. Dippel, E. J. van Breda, H. M.A. van Gemert, H. B. van der Worp, R. J. Meijer, L. J. Kappelle, and P. J. Koudstaal Effect of Paracetamol (Acetaminophen) on Body Temperature in Acute Ischemic Stroke : A Double-Blind, Randomized Phase II Clinical Trial Stroke, July 1, 2001; 32(7): 1607 - 1612. [Abstract] [Full Text] [PDF]

				J. Oliveira-Filho, M. A. Ezzeddine, A. Z. Segal, F. S. Buonanno, Y. Chang, C. S. Ogilvy, G. Rordorf, L. H. Schwamm, W. J. Koroshetz, and C. T. McDonald Fever in subarachnoid hemorrhage: Relationship to vasospasm and outcome Neurology, May 22, 2001; 56(10): 1299 - 1304. [Abstract] [Full Text] [PDF]

				S.A. Mayer, C. Commichau, N. Scarmeas, M. Presciutti, J. Bates, and D. Copeland Clinical trial of an air-circulating cooling blanket for fever control in critically ill neurologic patients Neurology, February 13, 2001; 56(3): 292 - 298. [Abstract] [Full Text] [PDF]

				H. Yanamoto, I. Nagata, Y. Niitsu, Z. Zhang, J.-H. Xue, N. Sakai, H. Kikuchi, and C. Iadecola Prolonged Mild Hypothermia Therapy Protects the Brain Against Permanent Focal Ischemia Editorial Comment Stroke, January 1, 2001; 32(1): 232 - 239. [Abstract] [Full Text] [PDF]

				A. Umemura, T. Suzuka, and K. Yamada Quantitative measurement of cerebral blood flow by 99mTc-HMPAO SPECT in acute ischaemic stroke: usefulness in determining therapeutic options J. Neurol. Neurosurg. Psychiatry, October 1, 2000; 69(4): 472 - 478. [Abstract] [Full Text] [PDF]

				D. Azzopardi, N. J. Robertson, F. M. Cowan, M. A. Rutherford, M. Rampling, and A. D. Edwards Pilot Study of Treatment With Whole Body Hypothermia for Neonatal Encephalopathy Pediatrics, October 1, 2000; 106(4): 684 - 694. [Abstract] [Full Text]

				S. A. Mayer, D. Copeland, G. L. Bernardini, B. Boden-Albala, L. Lennihan, S. Kossoff, and R. L. Sacco Cost and Outcome of Mechanical Ventilation for Life-Threatening Stroke Stroke, October 1, 2000; 31(10): 2346 - 2353. [Abstract] [Full Text] [PDF]

				L.P. Kammersgaard, B.H. Rasmussen, H.S. Jorgensen, J. Reith, U. Weber, and T.S. Olsen Feasibility and Safety of Inducing Modest Hypothermia in Awake Patients With Acute Stroke Through Surface Cooling: A Case-Control Study : The Copenhagen Stroke Study Stroke, September 1, 2000; 31(9): 2251 - 2256. [Abstract] [Full Text] [PDF]

				P. D. Schellinger, O. Jansen, J. B. Fiebach, S. Heiland, T. Steiner, S. Schwab, O. Pohlers, H. Ryssel, K. Sartor, and W. Hacke Monitoring Intravenous Recombinant Tissue Plasminogen Activator Thrombolysis for Acute Ischemic Stroke With Diffusion and Perfusion MRI Stroke, June 1, 2000; 31(6): 1318 - 1328. [Abstract] [Full Text] [PDF]

				P. Krafft, T. Frietsch, C. Lenz, A. Piepgras, W. Kuschinsky, K. F. Waschke, and C. Iadecola Mild and Moderate Hypothermia ({alpha}-Stat) Do Not Impair the Coupling Between Local Cerebral Blood Flow and Metabolism in Rats Editorial Comment Stroke, June 1, 2000; 31(6): 1393 - 1401. [Abstract] [Full Text] [PDF]

				R. Davenport and M. Dennis Neurological emergencies: acute stroke J. Neurol. Neurosurg. Psychiatry, March 1, 2000; 68(3): 277 - 288. [Abstract] [Full Text] [PDF]

				C. Hajat, S. Hajat, and P. Sharma Effects of Poststroke Pyrexia on Stroke Outcome : A Meta-Analysis of Studies in Patients Stroke, February 1, 2000; 31(2): 410 - 414. [Abstract] [Full Text] [PDF]

				S. Schwarz, K. Hafner, A. Aschoff, and S. Schwab Incidence and prognostic significance of fever following intracerebral hemorrhage Neurology, January 25, 2000; 54(2): 354 - 354. [Abstract] [Full Text] [PDF]

				H. Yanamoto, I. Nagata, I. Nakahara, N. Tohnai, Z. Zhang, H. Kikuchi, and C. Iadecola Combination of Intraischemic and Postischemic Hypothermia Provides Potent and Persistent Neuroprotection Against Temporary Focal Ischemia in Rats • Editorial Comment Stroke, December 1, 1999; 30(12): 2720 - 2726. [Abstract] [Full Text] [PDF]

				G DEVUYST and J BOGOUSSLAVSKY Recent progress in drug treatment for acute stroke J. Neurol. Neurosurg. Psychiatry, October 1, 1999; 67(4): 420 - 425. [Full Text] [PDF]

				R. Schmid-Elsaesser, E. Hungerhuber, S. Zausinger, A. Baethmann, H.-J. Reulen, and J. A. Zivin Combination Drug Therapy and Mild Hypothermia : A Promising Treatment Strategy for Reversible, Focal Cerebral Ischemia • Editorial Comment: A Promising Treatment Strategy for Reversible, Focal Cerebral Ischemia Stroke, September 1, 1999; 30 (9): e1891 - 1899. [Abstract] [Full Text] [PDF]

				S. Manzar, J. Castillo, A. Davalos, J. Marrugat, and M. Noya Body Temperature and Outcome of Asphyxiated Neonate • Response Stroke, May 1, 1999; 30(5): 1153 - 1153. [Full Text] [PDF]

				C. Berger, A. Annecke, A. Aschoff, M. Spranger, and S. Schwab Neurochemical Monitoring of Fatal Middle Cerebral Artery Infarction Stroke, February 1, 1999; 30(2): 460 - 463. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schwab, S. Articles by Hacke, W. Search for Related Content PubMed PubMed Citation Articles by Schwab, S. Articles by Hacke, W.