The first scientific report on clinical use of hypothermia was published in 1945. Fay [1] applied deep hypothermia (28° C) in patients after severe head trauma. The outcomes were satisfactory, even though several patients died due to arrhythmia and sepsis. In the 50ties, hypothermia was used in cerebral aneurysm surgeries [2, 3].

In the same period, first reports on the use of hypothermia following cardiac arrest were presented [4, 5, 6]. Nevertheless, hypothermia did not gain wider attention and popularity. The majority of the papers published then concerned deep hypothermia <30° C, which was associated with increased incidence of side effects and uncertain therapeutic benefits. In the 80ties, hypothermia became popular again. Many experimental animal studies were published, which showed the usefulness and higher safety of mild and moderate hypothermia (32-35° C) compared to deep hypothermia [7, 8] in the treatment of cerebral ischaemia. Since then, numerous attempts have been made to use neuroprotective effects of controlled hypothermia in various clinical situations.

NEUROPROTECTION OF HYPOTHERMIA

Neuroprotective effects of hypothermia result from the fact that a vast majority of damaging processes, which develop under ischaemic conditions are temperature-dependent; fever enhances while hypothermia inhibits them. Unlike some other suggested methods of neuroprotection, hypothermia seems to affect simultaneously many damage-inducing factors [9]. Firstly, a decrease in core temperature reduces the brain oxygen and glucose consumption. The cerebral cells do not have oxygen and glucose stores, which are necessary for the production of ATP. Sixty seconds of ischaemia is enough to reduce the ATP level in a neuron and impair the metabolic processes: decreased production of proteins and enhanced anaerobic metabolism, which leads to production of lactic acid and endo- as well as exogenous acidosis and impaired ion homeostasis inside the cell membranes [10]. Depolarization of synaptic membranes and influx of calcium ions to the cell leads to the release of huge amounts of stimulating neurotransmitters to the extr
acellular spaces, which results in prolonged and excessive stimulation of membranous glutamate receptors, activation of calcium channels and further extracellular calcium influx to the cells. This, in turn, leads to uncontrolled activation of Ca2+-dependent enzymes: proteases, phospholipases, NO synthase and others; as a result, cell proteins and lipids are digested, arachidonic acid metabolism triggered and production of reactive oxygen species increased. All these processes result in damage and subsequent necrosis of neurons. Ischaemic neurons also die due to apoptosis - programmed cell death [11]. It is believed that apoptosis of neurons is triggered by impaired energy production.

Hypothermia is estimated to decrease cerebral metabolism by 5-7% per every 1° Celsius [12, 13]. At decreased metabolism, the consumption of ATP is slowed down, despite the lack of glucose and oxygen supply, and ion pumps are efficient longer.

Hypothermia prevents apoptosis-related neuronal damage, most likely by inhibiting the caspase activation and mitochondrial dysfunction [14, 15]. Moreover, it reduces the release of glutamate inhibiting the processes of pathological activation of neurons and calcium ion influx to cells [16]. Additionally, the release of reactive oxygen species is decreased and peroxidation processes inhibited [17].

Hypothermia stabilizes the blood-brain barrier [18, 19] by sealing the neuronal membranes and reducing the permeability of microcirculation vessels [20], and decreases haemoglobin extravasation after head trauma [21]. Thus, cooling protects the brain against cytotoxic oedema and vasogenic oedema [22].

Neuroprotective effects of hypothermia may also result from its poor anticoagulative effects: in hypothermia, the blood platelet count is reduced and formation of fibrin impaired. Theoretically, this can prevent embolism of fine cerebral vessels [22]. Hypothermia diminishes the seizure activity – there are casuistic reports on its use in drug-resistant epilepsy [23].

The multidirectional mechanism of action of hypothermia offers a wide range of therapeutic options and justifies the attempts to use it in various clinical situations.

CLINICAL USE OF CONTROLLED HYPOTHERMIA

1. Cardiac arrest. The first attempts to use mild hypothermia in patients after cardiac arrest were made in the 50ties. In the 60ties, Rosomoff [6, 24] and Safar were the pioneers of experimental and clinical studies. In their classic publication [6], they recommended hypothermia for patients after cardiac arrest. The method did not gain wide popularity due to the side effects observed. In the 80ties, two randomized clinical trials were carried out and their results were published in 2002. The Australian study concerned 77 patients (43 treated with hypothermia). Hypothermia was initiated already in the ambulance; the body temperature of 33º C was achieved and maintained for 12 h. A better therapeutic outcome – defined as lack of or slight neurologic – deficit was observed amongst patients treated with hypothermia. There were no differences in survival between both groups [25]. The European study involved 273 patients (136 treated with hypothermia). Good therapeutic outcomes in the group treated with hypotherm
ia were found in 55% of cases vs 39% in the control group; the mortality rates were 41% vs 55%, respectively. In this study, core temperature of 32-34º C was maintained for 24 h [26].

According to the European Resuscitation Council and American Heart Association, hypothermia is recommended in unconscious patients with witnessed cardiac arrest when an ambulance arrived within 15 min, cardiac arrest developed during ventricular fibrillation or ventricular tachycardia and the time of spontaneous circulation return was shorter than 60 min. In such cases, hypothermia (32-33ºC) should be used as soon as possible and maintained for 12-24 h [27].

There are no unanimous opinions whether hypothermia is beneficial for patients with cardiac arrest with asystole. Nevertheless, some centres use hypothermia in all patients fulfilling the above-mentioned criteria, irrespective of the cardiac arrest mechanism [28].

2. Hypoxic-ischaemic encephalopathy in newborns. In recent years, three randomized, controlled, multi-centre studies were published [29, 30, 31], which demonstrated the efficacy and safety of controlled hypothermia in the treatment of newborns with symptoms of hypoxic-ischaemic encephalopathy. The analysis involved 491 patients in 47 centres. Hypothermia was started about 5 h after birth and maintained for 48-72 h. Substantially lower mortality rates and less severe neurological deficits were observed in the hypothermia group. In Poland, the pioneer report on hypothermia comes from the Department of Neurology, Polish Mother’s Health Centre – Research Institute in Łódz.  [32].

3. Craniocerebral trauma. The position of hypothermia for the treatment of patients after cardiac arrest and newborns with asphyxia is well established yet its use in head trauma patients remains controversial; clinical studies often provide conflicting results.

Hypothermia reduces the intracranial pressure (ICP) [33]; however, a decrease per se does not guarantee the survival of patients and beneficial neurologic outcomes. Two reviews of literature [34, 35] analysed 31 randomized controlled clinical studies about hypothermia published in the years 1992-2007. The results of studies were conflicting; some even proved harmful effects of hypothermia after head trauma. The authors of the reviews emphasize, however, that treatment failures are likely to be associated with improper use of hypothermia. Better outcomes and lower mortality rates were observed in the centres that instituted hypothermia early and maintained it until ICP stabilization rather than routinely for e.g. 24 h or 48 h. In hypothermia induced according to the pre-set protocol, there is a risk that patients will be re-warmed during increasing cerebral oedema. Moreover, better outcomes are reported by larger neurotrauma centres experienced in hypothermia and management of its complications. In the centres, which implemented hypothermia for the purposes of the multi-centre study, the results were worse.

The meta-analysis ordered by the Brain Trauma Foundation encompassed 13 clinical trials – in total, 1339 patients after craniocerebral trauma. Its results demonstrate that hypothermia reduces the mortality risk and improves the neurologic outcomes once used over the period >48 h, yet is associated with the risk of pneumonia [36]. Based on these results, the Brain Trauma Foundation and American Association of Neurological Surgeons allow cautious use of hypothermia in adult patients after head trauma as the second-line method if ICP cannot be reduced using analgesia, sedation, therapy with osmotically active drugs, and active ventricular drainage [37].

The use of hypothermia in children with traumas is similarly controversial. According to the American guidelines [38], hypothermia may be used as an alternative method of treatment of resistant ICP when the first-line therapy has failed, i.e. sedation, analgesia, ventricular drainage, osmotically active agents.

Recently, many reports suggest that hypothermia is harmful [39, 40]. Hutchison and co-workers [39] in the prospective, randomized study demonstrated that the use of hypothermia in children was associated with worse treatment outcomes. The discussion undertaken emphasized that in the study in question, hypothermia was achieved too late (on average after 10.3 h) and patients were routinely re-warmed after 24 h, irrespective of the clinical situation [41]. Rapid re- warming during increasing cerebral oedema might have induced complications. It seems that further clinical trials are needed to evaluate explicitly the effectiveness of hypothermia in children with severe craniocerebral trauma.

4. Ischaemic stroke. The mechanism of damage in stroke differs from that in global ischaemia: the area of total ischaemia leading to irreversible necrosis of neurons is surrounded by the region of hypoperfusion (penumbra), in which the cells are not completely damaged. Potentially, this region may be rescued; simultaneously it is more exposed to reperfusion-related damage. Theoretically, hypothermia by its multidirectional mechanism of action offers wider neuroprotective possibilities. However, controlled, randomized clinical trials proving the efficacy of such a strategy are lacking. The available studies do not demonstrate explicitly beneficial effects of hypothermia on treatment outcomes; those which show such effects are not randomized [42, 43].

On the other hand, digital CT scans reveal that hypothermia is effective for cerebral oedema accompanying the stroke [4].

5. Spinal cord injury. Interest in the use of hypothermia in the treatment of spinal cord injuries started in the 70ties. Several experimental animal studies were published demonstrating beneficial effects of hypothermia on the return of motor and sensory function after induced spinal cord damage. Based on those positive results the attempts were made to use hypothermia in humans. In the 80ties, studies were published about 52 cases of hypothermia use in patients with traumas. In 48% of them (!), the neurologic function improved [45]. That was, however, the uncontrolled clinical report and positive treatment outcomes were not analysed as to possible spontaneous improvement of the spinal cord function. No reliable controlled studies concerning the effects of therapeutic hypothermia in patients with spinal cord damage have been published since then [46].

6. Acute hepatic failure. Cerebral oedema is a potentially life-threatening complication of acute hepatic failure. Patients with a fulminant form of the disease are most prone to the development of oedema, e.g. intoxicated with paracetamol. In severe cases, ICP develops and patients are at risk of brain herniation. There are several reports confirming the efficacy of hypothermia in the treatment of ICP in patients with acute hepatic failure. Their authors recommend this management to keep patients alive while awaiting liver transplantation [47, 48].

PRACTICAL ASPECTS OF THERAPEUTIC HYPOTHERMIA

In clinical practice, the therapy with controlled hypothermia means an intentional and controlled reduction in core temperature to 34-35.9º C – mild hypothermia or to 32 – 33.9° C – moderate hypothermia [22].

1. Induction of hypothermia. There are two methods to induce hypothermia: superficial and deep cooling [49].

The former is achieved by immersion in cold water (currently no longer used) or the use of fans, cooling blankets filled with cold air or water, water or alcohol aerosols, application of ice packs. For the treatment of newborns with ischaemic-hypoxic encephalopathy, cooling helmets are used. Some centres have special beds for hypothermia treatment.

The methods of deep cooling include: the use of vascular catheters with the balloon filled with cold solution of 0.9% NaCl, transfusions of cold fluids and application of antipyretic drugs. Extracorporeal circulation and peritoneal lavage are less common.

The optimal rate of cooling is not known. Generally, the quicker the cooling, the slighter the adverse effects. The main problems associated with cooling are shivers and vasospasms. In unconscious patients, shivers cause an increase in oxygen consumption and in metabolism – even by 40-100% [28] and accelerated heart rate. Patients feel unpleasant sensations. Shivers are eliminated effectively and quickly using analgesics and sedatives: fentanyl, pethidine, propofol, midazolam, and clonidine or magnesium sulphate [22].  Muscle relaxants may also be applied, if necessary. One should be aware, however, that relaxation can mask  the seizure activity or too shallow sedation. If muscle relaxants are used, some authors recommend continuous monitoring of bioelectric brain activity, e.g. using the BIS method [50].

Since metabolism and oxygen consumption are reduced, frequent gasometry and correction of ventilator set values are needed to avoid hyperventilation and cerebral vasospasms.

In hypothermia, tissue resistance to insulin develops, which in consequence leads to hyperglycaemia, requiring appropriate correction of glucose and/or insulin supply.

Hypothermia leads to relative hypovolaemia and dehydration due to “cold diuresis” [22]. The causes of polyuria in hypothermia include increased venous return and release of atrial natriuretic hormone, decreased release of antidiuretic hormone and renal tubule dysfunction. To prevent hypotension, accurate fluid balance, control of CVP and hourly diuresis are recommended.

Hypothermia is characterized by electrolyte disturbances: hypokalaemia, hypomagnesaemia and hypophosphataemia [51]. Hypokalaemia is particularly dangerous; in order to avoid it, potassium concentration should be determined every 3-4 h.

To provide safe hypothermia therapy, vital functions ought to be thoroughly and continuously monitored: ECG, SpO2, SAP/DAP by direct method, CVP, ETCO2 and hourly diuresis. Controlled hypothermia obviously requires proper monitoring of temperature. Measurements in the pulmonary artery and jugular vein bulb are most reliable – feasible yet troublesome. In practice, measurements are made in the oesophagus, oronasal cavity, bladder, rectum or external auditory meatus near the tympanic membrane. The forehead measurements are relatively reliable and correlate with the temperature measured using the needle sensor on the frontal lobe [49]. The axillary determinations are considered completely unreliable.

2. Maintenance of hypothermia. During this period the patient`s condition stabilizes. The major problems regard:

• circulatory stability – in mild hypothermia in a calm normovolemic patient, the heart rate decreases, myocardial contractility improves and blood pressure is normal or slightly elevated. Deep hypothermia reduces myocardial contractility, slows down the heart rate and predisposes to arrhythmia;

• coagulation disorders and increased risk of haemorrhage [49]. A decrease in temperature <35º C results in platelet dysfunction and decreased platelet count; <33º C – blood coagulation is impaired due to unfavourable effects on thrombin and plasminogen inhibitors. It should be emphasized that coagulopathy may develop despite the lack of evident changes in the coagulogram – laboratory tests are carried out at 37º C. Clotting disorders are treated by transfusion of blood platelet cells and fresh frozen plasma, particularly when surgical procedures are considered;

• impaired motor activity of the alimentary tract, increased hepatic enzymes, hyperglycaemia, elevated levels of lactates, and reduced granulocyte count – in deep hypothermia.

The optimal timing for hypothermia has not been established. In patients after cardiac arrest, positive outcomes are achieved after 12-24 h [25, 26]. In newborns with asphyxia, hypothermia is usually used for 72 h [31], in hepatic failure with cerebral oedema even for 5 days [47, 48].

3. Re-warming. The induction of hypothermia should be quick yet the return to normal body temperature extremely slow and lasting 12-24 h. The mean rate of temperature increase should be 0.25-0.33° C h-1 [22, 50]. A sudden increase in brain temperature is likely to cause fluctuations in cerebral flow inducing increased intra-cranial pressure, herniation or even death [52, 53].

Peripheral vasodilation can cause hypotension. Increased energy demands are associated with the risk of hypoglycaemia, and shifts of ions are likely to lead to hyperkalaemia. Rapid re-warming may lead to „contre-coup” hyperthermia. It is well known that fever is a relevant risk factor deteriorating the prognosis after cardiac arrest, stroke or brain damage [34, 54, 55].

POST-HYPOTHERMIA COMPLICATIONS

Hypothermia affects the immune functions; reduced production of cytokines, and free oxygen radicals, plus impaired leukocyte function decide about its positive neuroprotective effects. At the same time, impairment of some protective processes results in increased risk of infections, particularly pneumonia [36]. It is believed that this concerns patients treated with hypothermia >48 h. The care of patients in hypothermia requires special sanitary regime. Thorough physiotherapy is necessary, even prophylactic antibiotic therapy. The diagnosed infection should be aggressively treated.

Another relevant complication is decubital lesions [49], which is mainly caused by vasospasm of skin vesels.

The demonstrated multidirectional neuroptotective effects of hypothermia make it useful in many clinical situations. Based on the available knowledge, hypothermia can be recommended for patients after cardiac arrest and in newborns with asphyxia; it is also acceptable for the management of treatment-resistant ICP after head trauma. The hypothermia treatment is not easy and is associated with dangerous adverse side effects. The key to success is not its institution but proper management, thorough observation and immediate reactions to changes in the processes of cooling and re-warming.

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REFERENCES

1.    Fay T: Observations on generalized refrigeration in cases of severe cerebral trauma. Assoc Res Nerv Ment Dis Proc 1943; 24: 611-619.

2.    Botterell EH, Lougheed WM, Morley TP, Vandewater SL: Hypothermia in the surgical treatment of ruptured intracranial aneurysms. J Neurosurg 1958; 15: 4-18.

3.    Botterell EH, Lougheed WM, Scott JW, Vandewater SL: Hypothermia, and interruption of carotid, or carotid and vertebral circulation, in the surgical management of intracranial aneurysms. J Neurosurg 1956; 13: 1-42.

4.    Williams GR Jr, Spencer FC: The clinical use of hypothermia following cardiac arrest. Ann Surg 1958; 148: 462-468.

5.    Benson DW, Williams GR Jr, Spencer FC, Yates AJ: The use of hypothermia after cardiac arrest. Anesth Analg 1959; 38: 423-428.

6.    Rosomoff HL, Safar P: Management of the comatose patient. Clin Anesth 1965; 1: 244-258

7.    Berntman L, Welsh FA, Harp JR: Cerebral protective effect of low-grade hypothermia. Anesthesiology 1981; 55: 495-498.

8.    Chopp M, Knight R, Tidwell CD, Helpern JA, Brown E, Welch KM: The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat: comparison to normothermia and hyperthermia.  J Cereb Blood Flow Metab 1989; 9: 141-148.

9.    Zhao H, Steinberg GK, Sapolsky RM: General versus specific actions of mild-moderate hypothermia in attenuating cerebral ischemic damage. J Cereb Blood Flow Metab 2007; 27: 1879-1894.

10.    MacDonald RL, Stoodley M: Pathophysiology of cerebral ischemia. Neurol Med Chir (Tokyo) 1998; 38: 1-11.

11.    Springer JE: Apoptotic cell death following traumatic injury to the central nervous system. J Biochem Mol Biol 2002; 35: 94-105.

12.    Ehrlich MP, McCullough JN, Zhang N, Weisz DJ, Juvonen T, Bodian CA, Griepp RB: Effect of hypothermia on cerebral blood flow and metabolism in the pig. Ann Thorac Surg 2002; 73: 191-197.

13.    Erecinska M, Thoresen M, Silver IA: Effects of hypothermia on energy metabolism in mammalian central nervous system. J Cereb Blood Flow Metab 2003; 23: 513-530.

14.    Xu L, Yenari MA, Steinberg GK, Giffard RG: Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J Cereb Blood Flow Metab 2002; 22: 21-28.

15.    Zhao H, Yenari MA, Cheng D, Sapolsky RM, Steinberg GK: Biphasic cytochrome C release after transient global ischemia and its inhibition by hypothermia. J Cereb Blood Flow Metab 2005; 25: 1119-1129.

16.    Globus MY, Alonso O, Dietrich WD, Busto R, Ginsberg MD: Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. J Neurochem 1995; 65: 1704-1711.

17.    Bayir H, Adelson PD, Wisniewski SR, Shore P, Lai Y, Brown D, Janesko-Feldman KL, Kagan VE, Kochanek PM: Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children. Crit Care Med 2009; 37: 689-695.

18.    Lotocki G, de Rivero Vaccari JP, Perez ER, Sanchez-Molano J, Furones-Alonso O, Bramlett HM, Dietrich WD: Alterations in blood-brain barrier permeability to large and small molecules and leukocyte accumulation after traumatic brain injury: effects of post-traumatic hypothermia. J Neurotrauma 2009; 26: 1123-1134.

19.    Chi OZ, Liu X, Weiss HR: Effects of mild hypothermia on blood-brain barrier disruption during isoflurane or pentobarbital anesthesia. Anesthesiology 2001; 95: 933-938.

20.    Jurkovich GJ, Pitt RM, Curreri PW, Granger DN: Hypothermia prevents increased capillary permeability following ischemia-reperfusion injury. J Surg Res 1988; 44: 514-521.

21.    Kinoshita K, Chatzipanteli K, Alonso OF, Howard M, Dietrich WD: The effect of brain temperature on hemoglobin extravasation after traumatic brain injury. J Neurosurg 2002; 97: 945-953.

22.    Polderman KH: Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med 2009; 37(Suppl. 7): S186-S202.

23.     Corry JJ, Dhar R, Murphy T, Diringer MN: Hypothermia for refractory status epilepticus. Neurocrit Care 2008; 9: 189-197.

24.    Rosomoff HL: Experimental brain injury during hypothermia. J Neurosurg 1959; 16: 177-187.

25.    Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K: Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346: 557-563.

26.    Hypothermia after Cardiac Arrest Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346: 549-556.

27.    Nolan JP, Deakin CD, Soar J, Böttiger BW, Smith G: European Resuscitation Council. European Resuscitation Council guidelines for resuscitation 2005. Section 4. Adult advanced life support. Resuscitation. 2005; 67 (Suppl. 1): S39-86.

28.    Polderman KH: Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality. Part 1: Indications and evidence. Intensive Care Med 2004; 30: 556-575.

29.    Eicher DJ, Wagner CL, Katikaneni LP, Hulsey TC, Bass WT, Kaufman DA, Horgan MJ, Languani S, Bhatia JJ, Givelichian LM, Sankaran K, Yager JY: Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 2005; 32: 11-17.

30.    Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ: Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365: 663-670.

31.    Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH: Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353: 1574-1584.

32.    Gulczyńska E, Cyranowicz B, Nowiczewski M, Talar T, Lerch E, Wilk E, Kęsiak M: Selektywne chłodzenie mózgu z umiarkowaną hipotermią ciała w leczeniu noworodków z encefalopatią niedokrwienno-niedotlenieniową-pierwsze doświadczenia w Polsce. V Kongres PTMP – Materiały zjazdowe, 2009.

33.    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.

34.    Polderman KH: Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet 2008; 371: 1955-1969.

35.    Shann F: Hypothermia for traumatic brain injury: how soon, how cold, and how long? Lancet 2003; 362: 1950-1951.

36.    Peterson K, Carson S, Carney N: Hypothermia treatment for traumatic brain injury: a systematic review and meta-analysis. J Neurotrauma 2008; 25: 62-71.

37.    Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons: Guidelines for the management of severe traumatic brain injury. J Neurotrauma. 2007; 24 (Suppl. 1): S1-106.

38.    American Association for the Surgery of Trauma; Child Neurology Society; International Society for Pediatric Neurosurgery; International Trauma Anesthesia and Critical Care Society; Society of Critical Care Medicine; World Federation of Pediatric Intensive and Critical Care Societies; National Center for Medical Rehabilitation Research; National Institute of Child Health and Human Development; National Institute of Neurological Disorders and Stroke; Synthes USA; International Brain Injury Association: Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents.  J Trauma. 2003; 54 (Suppl. 6): S235-310.

39.    Hutchison JS, Ward RE, Lacroix J: Hypothermia therapy after traumatic brain injury in children. N Engl J Med 2008; 358: 2447-2456.

40.    Adelson PD, Ragheb J, Kanev P: Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children. Neurosurgery 2005; 56: 740-754.

41.    Polderman KH, Mayer SA, Menon D: Hypothermia therapy after traumatic brain injury in children. N Engl J Med 2008; 359: 1178.

42.    De Georgia MA, Krieger DW, Abou-Chebl A, Devlin TG, Jauss M, Davis SM, Koroshetz WJ, Rordorf G, Warach S: Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling. Neurology 2004; 63: 312-317.

43.    Krieger DW, De Georgia MA, Abou-Chebl A, Andrefsky JC, Sila CA, Katzan IL, Mayberg MR, Furlan AJ: Cooling for Acute Ischemic Brain Damage (COOL AID): an open pilot study of induced hypothermia in acute ischemic stroke. Stroke 2001; 32: 1847-1854.

44.    Guluma KZ, Oh H, Yu SW, Meyer BC, Rapp K, Lyden PD: Effect of endovascular hypothermia on acute ischemic edema: morphometric analysis of the ICTuS trial. Neurocrit Care 2008; 8: 42-47.

45.    Janssen L, Hansebout RR: Pathogenesis of spinal cord injury and newer treatments. Spine (Phila Pa 1976) 1989; 14: 23-32.

46.    Kwon BK, Mann C, Sohn HM, Hilibrand AS, Phillips FM, Wang JC, Fehlings MG: NASS Section on Biologics. Hypothermia for spinal cord injury. Spine J 2008; 8: 859-874.

47.    Jalan R, Olde Damink SW, Deutz NE, Hayes PC, Lee A: Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension. Gastroenterology 2004; 127: 1338-1346.

48.    Jalan R, O Damink SW, Deutz NE, Lee A, Hayes PC: Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure. Lancet 1999; 354: 1164-1168.

49.    Polderman KH, Herold I: Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med 2009; 37: 1101-1120.

50.    Seder DB, Van der Kloot TE: Methods of cooling: Practical aspects of therapeutic temperature management. Crit Care Med 2009; 37 (Suppl.): S211-218.

51.    Polderman KH, Peerdeman SM, Girbes AR: Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury. J Neurosurg. 2001; 94: 697-705.

52.    Lavinio A, Timofeev I, Nortje J, Outtrim J, Smielewski P, Gupta A, Hutchinson PJ, Matta BF, Pickard JD, Menon D, Czosnyka M: Cerebrovascular reactivity during hypothermia and rewarming. Br J Anaesth 2007; 99: 237-244.

53.    Steiner T, Friede T, Aschoff A, Schellinger PD, Schwab S, Hacke W: Effect and feasibility of controlled rewarming after moderate hypothermia in stroke patients with malignant infarction of the middle cerebral artery. Stroke 2001; 32: 2833-2835.

54.    Zeiner A, Holzer M, Sterz F, Schörkhuber W, Eisenburger P, Havel C, Kliegel A, Laggner AN: Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med 2001; 161: 2007-2012.

55.    Hajat C, Hajat S, Sharma P: Effects of poststroke pyrexia on stroke outcome: a meta-analysis of studies in patients. Stroke 2000; 31: 410-414.

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Address:

*Izabela Pągowska-Klimek
Zakład Anestezjologii i Intensywnej Terapii Medycznej
ICZMP Łódź
ul. Rzgowska 281/289, 93-338 Łódź
e-mail: izabela.pagowska@neostrada.pl

Received: 29.10.2009
Accepted: 30.03.2010