Spontaneous Hypothermia Research Articles

MILD HYPOTHERMIA AND BRAIN TISSUE OXYGENATION IN NEUROSURGICAL PATIENTS

S238 INTRODUCTION: Mild hypothermia is being advocated for brain protection in patients at risk for ischemia in neuroanesthesia and neurointensive care. However, its influence on brain oxygenation and metabolism in humans is not fully understood. Therefore, we studied the effects of therapeutic cooling on brain substrates and metabolites in severely head injured patients. METHODS: In this study we measured continuously oxygen, CO2, pH, and temperature in the brain tissue as well as hourly brain glucose and lactate. A multiparameter sensor was inserted into brain tissue, along with a ventriculostomy catheter and a microdialysis probe in 60 severely head injured patients. A xenon enhanced CBF-CT study was performed between days 1-2 and 3-5, after trauma. RESULTS: In most patients brain oxygen was initially low and progressively increased over the monitoring period to a steady state level around 30-40 mmHg. Patients who received therapeutic cooling (n=33, Tbr=35.3 +/- 0.5[degree sign]C) had a significantly lower brain CO2, glucose, and lactate, whereas brain pH and CPP were significantly higher, compared to normal temperature (Tbr=36.9 +/- 0.4[degree sign]C, p<0.01). Their brain oxygen decreased, but stayed above 30 mmHg. However, patients with spontaneous hypothermia (Tbr=34.4 +/- 1.5[degree sign]C), had a high ICP and lactate, whereas brain oxygen, pH, and glucose were significantly lower compared to normothermia (p<0.01). The mean CBF in patients with spontaneous hypothermia was significantly lower than in normothermic patients (17 ml/100g/min versus 37 ml/100g/min). DISCUSSION: A fuller understanding of dynamic factors affecting brain metabolism and substrate delivery is possible with extended neuromonitoring. Therapeutic cooling reduces substrate delivery and metabolism in severely head injured patients. However, spontaneous brain hypothermia is characterized by markedly abnormal brain metabolites, and carries a poor prognosis.

Recurrent coma

Recurrent episodes of coma are usually associated with a metabolic disorder. A healthy 9-year-old boy of normal intellect and intact corpus callosum on neuroimaging had recurrent episodes of coma associated with profound spontaneous hypothermia. An evaluation, differential diagnosis and insights into the pathogenesis of this disorder are discussed.

Skin blood flow and autonomic reactivity in human poikilothermia

Autonomic reactivity is pivotal in maintaining a constant body core temperature. Skin vasomotor reflexes and cardiovascular reactivity were investigated in four women (aged 28-37 years) with acquired poikilothermia, during steady-state spontaneous hypothermia (rectal temperature (Tr) = 33.7 +/- 1.0 degrees C [mean +/- SD]) and steady-state normothermia (Tr = 36.7 +/- 0.3 degrees C), as well as in 12 normothermic control subjects. Baseline finger temperature (Tf) during hypothermia was significantly lower than during normothermia (Tf = 32.4 +/- 1.2 compared with 36.2 +/- 0.3 degrees C, respectively), and than in the controls (Tf = 34.8 +/- 0.8 degrees C). No significant differences in baseline skin blood flow and forearm blood flow were found between subjects during hypothermia or normothermia and controls, suggesting a failure of sympathetic drive to counter-regulate hypothermia in the subjects. Skin vasoconstrictor responses to the contralateral cooling test and neck cooling test were markedly attenuated in three subjects, and to the finger cooling test in two subjects, during normothermia compared with hypothermia. Blood pressure responses to the Valsalva manoeuvre and head-up tilting were normal in all subjects, whereas the heart rate response to head-up tilting was blunted in three subjects during hypothermia. The responses of blood pressure and forearm blood flow to the cold pressor test in the subjects during both thermal conditions were comparable with the controls. We conclude that in our subjects, without generalized autonomic failure, poikilothermia has to be attributed predominantly to disorders of the central thermoregulatory pathways. Our findings during hypothermia and normothermia indicate that variations in core and skin temperature significantly affect skin vasomotor reactivity.

Oxygen dynamics and induced hypothermia in sepsis

The vital distinction between induced and spontaneous hypothermia [l] is highlighted by Villar and Slutsky’s study of moribund septic patients with adult respiratory distress syndrome (ARDS) [2]. The favourable impact of induced hypothermia in this series raises intriguing questions. What factor(s) were responsible for this outcome and why was there no reduction in total oxygen consumption (Vo, rota,) with the fall in temperature, in contrast to another encouraging report [3]? If we accept oxygen imbalance (02 imbalance) (hypoxia) as a major, though not the only factor [4,5] in the development of multiple organ dysfunction and finally multiple organ failure, we can reasonably postulate improved vital organ O2 balance, and hence improved vital organ function, as one major benefit of induced hypothermia. But this improved O2 balance may not have been accompanied by a fall in VO, total for at least two and even three possible reasons. The most attractive explanation lies in the concept of oxygen supply dependency (Fig. 1) and its consequence, tissue hypoxia. This condition was very likely present in these critically ill patients [2], septic shock and metabolic acidosis being two of the criteria for their inclusion in the study. Schumacker et al. [6] have shown experimentally t 40°C

Episodic spontaneous hypothermia with hyperhidrosis: Implications for pathogenesis

Unprovoked hypothermia is an unusual presenting sign. When occurring with diaphoresis it has been referred to as episodic spontaneous hypothermia with hyperhidrosis. Earlier reports described episodic, spontaneous hypothermia with hyperhidrosis in patients with agenesis of the corpus callosum and postulated a midline congenital malformation of the central nervous system. Since then, various endocrine, electrolyte, autonomic, and sleep disturbances have been described but the etiology remains undetermined. Three unrelated children are reported each of whom had an intact corpus callosum and normal endocrine function. Shivering was consistently absent despite marked symptomatic hypothermia. One child had spontaneous resolution of episodic spontaneous hypothermia with hyperhidrosis and two children responded to the antiserotonergic, cyproheptadine. It is hypothesized that specific serotonergic dysfunction in the anterior hypothalamic extrapyramidal shivering mechanism is central in the pathogenesis of this condition.

Hypothalamic dysfunction in a child: A distinct syndrome?

We report the case of a 9-year-old girl with multiple problems due to hypothalamic dysfunction of obscure origin: apnoeic spells, behavioural problems, developmental delay, hypodipsia with bouts of hypernatraemia, episodes of spontaneous hypothermia, obesity, petit-mal seizures, non-progressive precocious puberty, absence of respiratory response to CO2 and probably insensitivity of hyposensitivity to pain. She also had hyperprolactinaemia and decreased human growth hormone secretion. Hypothyroidism of central origin and hyposecretion of cortisol were also present. Multiple brain CT-scans failed to reveal any tumour or other anatomical abnormality. Her clinical course was improved initially by treatment with clomipramine, but she died suddenly, and the autopsy failed to disclose any anatomical lesion. We compare this case with three similar previously reported cases.

Heating of the brain to maintain normothermia during ischemia aggravates brain injury in the rat.

During brain ischemia temperature spontaneously declines. In animal experiments this decline is frequently prevented by stabilizing the temperature at the pre-ischemic level, using an external heat source. The present study examines whether this procedure influences the severity of ischemic injury. Wistar rats were submitted to 30-min four-vessel occlusion followed by 7 days recirculation. During ischemia and the 1st h of recirculation various systemic and electrophysiological variables were recorded. Seven days after the ischemia brains were perfusion-fixed for light microscopical examination. Three brain temperature profiles were compared: spontaneous decline of brain temperature during ischemia from 36 degrees to 31 degrees C (spontaneous hypothermia; n = 5); constant brain temperature of 30 degrees C induced by selective head cooling (induced hypothermia; n = 5); and constant brain temperature of 36 degrees C induced by selective head heating (normothermia; n = 5). Core temperature was maintained constant at 37 degrees C in all groups. In spontaneous hypothermia, 19% of CA1 neurons survived after 30-min ischemia. Induced hypothermia significantly increased this percentage to 69% (P < 0.05); maintenance of brain temperature at normothermia decreased neuronal survival to 1%. Normothermia also led to morphological injury outside the vulnerable regions, an increase in mortality, marked loss of body weight and a prolongation of the electroencephalographic suppression. These findings demonstrate that stabilizing brain temperature at a constant normothermic level by an external heart source introduces an aggravating pathological element that may interfere in an unpredictable way with the manifestation or treatment of ischemic injury.

Temperature effect on immunostaining of microtubule-associated protein 2 and synaptophysin after 30 minutes of forebrain ischemia in rat.

The regional distribution of the postsynaptic microtubule-associated protein 2 (MAP2) and the presynaptic marker protein synaptophysin was investigated by immunohistochemistry in brains of rats submitted to 30-min forebrain ischemia by four-vessel occlusion. The following brain temperature profiles during ischemia were compared: (1) constant brain temperature of 36 degrees C (normothermia; n = 5); (2) spontaneous temperature decline from 36 degrees to 31 degrees C (spontaneous hypothermia; n = 5) and (3) constant temperature of 30 degrees C (induced hypothermia; n = 5). Normothermia was produced by exposing the ischemic head to an external heat source, and induced hypothermia by cooling the head with liquid nitrogen vapours. Sham-operated animals were either kept at ambient temperature or exposed to the same heat source, as required for maintaining normothermia during ischemia. Seven days after sham operation or ischemia, brains were fixed by perfusion and processed for immunohistochemistry using monoclonal antibodies against MAP2 and synaptic vesicle-specific protein (synaptophysin). Normothermic ischemia resulted in complete loss of MAP2 immunostaining in the whole hippocampus, spontaneous hypothermic ischemia in complete loss of MAP2 in CA1 sector, and induced hypothermic ischemia only in variable loss of MAP2 in CA1 sector. Post-ischemic immunostaining of synaptophysin revealed a temperature-dependent increase in stratum lacunosum-moleculare of CA1 sector, the density of which correlated inversely with MAP2 staining. Comparison with morphological alterations showed a close relationship between loss of MAP2 staining and histological injury. The post-ischemic activation of synaptophysin may reflect regenerative processes associated with synaptic remodelling and, therefore, is an indirect marker of the severity of ischemic injury.

Thermoregulation and afterdrop during hypothermia in patients with poikilothermia

The pathophysiology of afterdrop of core temperature during rewarming in patients with induced or accidental hypothermia remains controversial. We studied the effect of cooling and rewarming in four female patients with acquired poikilothermia and in four normal females. Exposure to cold air (16.5 degrees C) induced shivering and adequate vasoconstriction in normal individuals, without a fall in rectal temperature (Tr; 36.3 +/- 0.2 degrees C [mean +/- SD]); subsequent heating (40 degrees C) induced a rise in Tr to 37.0 +/- 0.3 degrees C and generalized sweating. The four patients all had spontaneous hypothermia (Tr 34.1 +/- 0.9 degrees C) before cooling. Tr decreased by 0.3-0.9 degrees C during cold exposure, and a marked afterdrop of Tr (0.3-0.5 degrees C) occurred during rewarming: this did not occur in normal individuals. Cooling failed to induce shivering and vasoconstriction in three patients. No patient showed visible sweating during heating despite a Tr of up to 38.0-38.5 degrees C and skin temperature of up to 37.7-38.5 degrees C. The basal metabolic rate was decreased by 71-82% in all patients during steady-state hypothermia and remained lowered during normothermia in two patients. We conclude that during hypothermia three of the four patients showed severe disorders of peripheral vasomotor function and shivering response. These data provide evidence for thermal conduction as the major mechanism of afterdrop during hypothermia.

The effects of KR-10876, a new quinolone antimicrobial agent, on the central nervous system

To evaluate KR-10876, a new fluoroquinolone antibacterial agent, its effects on the central nervous system (CNS) were investigated in mice as part of pharmacological study, and the results were compared with those for ciprofloxacin and ofloxacin, two prototypes of quinolone antibacterial agents. All the parameters indicative of CNS function and acute toxicity were measured by close observation of the animals at regular time intervals after oral treatment of test compounds. KR-10876, ciprofloxacin and ofloxacin exerted a dose-dependent effect on the CNS functions studied. KR-10876 did not have any effects on the parameters measured at lower dose (100, 300 mg/kg, p.o.), but at high dose (1,000 mg/kg, p.o.), it caused ptosis, suppressed spontaneous locomotor activity, hypothermia, and prolonged hexobarbital-induced sleeping time. KR-10876 also had a slight effect on motor coordination only at high dose. Simialr to ciprofloxacin and ofloxacin, KR-10876 did not protect mice from pentylenetetrazol-, strychnine-, and electroshock-inducedl convulsions at doses tested. These findings demonstrate that KR-10876 affects CNS functions only at high doses. The rank order for effects is ofloxacin≥KR-10876>ciprofloxacin.

Sensitivity of isovolumic relaxation to hypothermia during myocardial infarction

Effects of moderate spontaneous hypothermia on left ventricular systolic and diastolic function during acute myocardial infarction were documented in 17 anesthetized dogs with micromanometric pressure and ventriculographic dimension recordings acquired at baseline and at 1 and 3 h after coronary occlusion. In Group 1 (n = 5), core temperature was allowed to decline spontaneously. In Groups 2 (n = 6) and 3 (n = 6), core temperature was maintained at normothermic levels. Hypothermia impaired isovolumic relaxation markedly despite its lack of effect on ventricular volumes or ejection fraction. At 32.3 °C, τ1/2, defined as the time needed for the left ventricular pressure at the time of peak negative rate of change of left ventricular pressure (dPdt) to fall by 50%, was increased by 129% 3 h after occlusion. In addition, at this temperature significant changes were found in heart rate, cardiac output, minute work, peak positive and peak negative dPdt, systolic ejection time, mean velocity of circumferential fiber shortening, mean aortic pressure and end-diastolic pressure.Thus, hypothermia evolving under conditions of general anesthesia profoundly alters left ventricular function in the setting of acute myocardial infarction, a phenomenon that requires consideration and control in studies of myocardial ischemia and left ventricular function in experimental animals.

Changes of body temperature and heat in cardiac surgical patients.

Changes in body temperature were assessed in ten adult patients undergoing surgery involving cardiopulmonary bypass (CPB) and induced hypothermia. Intraoperatively, in comparable time intervals before CPB and after rewarming, the patients lost body heat. Between the time of induction of anaesthesia and CPB, the temperature of blood in the pulmonary artery fell 1.46 (SD 0.28 degrees C); between CPB and the end of surgery the fall was 1.55 (SD 0.86 degrees C). The extent of spontaneous hypothermia did not correlate with the amount of subcutaneous fat. Hypothermia was induced to obtain a stable deep body temperature of 27.2 (SD 1.3) degrees C, when mean skin temperature averaged 2 degrees C higher. The CPB machine returned approximately 2000 kJ of heat in the rewarming period, to produce pulmonary artery and mean skin temperatures of 37.1 (SD 0.7) degrees C and 31.4 (SD 2.1) degrees C respectively. Intraoperative deep body temperatures demonstrated the expected exponential relationship with metabolic rate. Postoperatively, increase in metabolic rate was associated with rising deep body and skin temperatures. Low resistance to the flow of heat toward the skin surface was demonstrated by low postoperative values for thermal insulation, which may indicate good peripheral perfusion seen during continuing vasodilator therapy.

Diencephalic epilepsy in a patient with agenesis of the corpus callosum confirmed by computerised axial tomography

A case of diencephalic epilepsy is described in whom stereotyped attacks of spontaneous hypothermia and diaphoresis occurred over a 20 year period. No abnormality of the hypothalamo-pituitary-adrenal axis was found, and there was no evidence of an intracranial mass lesion. Pneumoencephalography and computerised axial tomography (EMI scan) demonstrated agenesis of the corpus callosum.

Accidental hypothermia and impaired temperature homoeostasis in the elderly.

A longitudinal study of the age-related decline in thermoregulatory capacity was made in 47 elderly people to try to identify those at risk from spontaneous hypothermia. During the winters of 1971-2 and 1975-6 environmental and body temperature profiles were obtained in the home, and thermoregulatory function was investigated by cooling and warming tests. Environmental temperature and socioeconomic conditions had not changed but the body core-shell temperature gradients were smaller in 1976, indicating progressive thermoregulatory impairment. People at risk of developing hypothermia also seem to have low resting peripheral blood flows, a nonconstrictor pattern of vasomotor response to cold, and a higher incidence of orthostatic hypotension.

Fievre Et Problemes Infectieux En Reanimation Medicale

SummaryThe authors have looked for fever and infections in a hundred consecutive cases treated in a medical intensive care unit. These patients suffered from severe intoxication, respiratory insufficiency, myocardial infarction, neurological diseases or endocrine disorders. Sixty-seven patients had fever, due to infection in at least 41 cases, 35 of which had a respiratory infection. Most of the patients with non-infectious fever had a myocardial necrosis or a cerebral affection. Twenty-seven patients acquired an infection within the unit ; these hospital-acquired infections are mainly due to fungi and to Gram-negative organisms. Many factors contribute to contaminate the patients : venous and urinary catheters, artificial ventilation, coma, spontaneous hypothermia, antibiotics, corticoids, etc. The main principles of the prevention of infections in intensive therapy units are recalled.

Intermittent hypothermia. Independence of central and reflex thermoregulatory mechanisms.

Three patients who had suffered episodes of spontaneous hypothermia are described. Circulatory control was normal for their age but there was evidence of a persistent defect of thermoregulatory mechanisms. In all patients vascular thermoregulatory reflexes dependent upon peripheral receptors were active and in two patients reflex shivering could be obtained. There appeared, however, to be a failure of central thermoregulation as the vascular reflexes were active at abnormally low central temperatures and a fall in central temperature did not initiate shivering. It is concluded that in patients who have suffered spontaneous hypothermia there may be a persistent defect of central mechanisms subserving vasomotion and shivering, although thermoregulatory reflexes dependent upon peripheral receptors can be active. The reflex pathways for thermoregulation in man therefore have a separate integrity, physiologically independent of the central thermoregulatory mechanisms.

Agenesis of the corpus callosum associated with relapsing hypothermia. A clinico-pathological report.

A 41 year old man had recurrent hypothermia with loss of consciousness which eventually became permanent. There was agenesis of the corpus callosum, with no evidence of dysfunction of the hypothalamo pituitary axis. Autopsy confirmed the agenesis, and showed intense fibrillary gliosis restricted to the arcuate nucleus and premammillary area, which may account for the thermoregulatory disturbance. The association of these hypothalamic lesions with congenital absence of the corpus callosum would seem a mere coincidence were it not for the striking clinical similarities between this case and others previously published. It is suggested that agenesis of the corpus callosum should be looked for in cases of unexplained spontaneous hypothermia.

Prolonged Spontaneous Hypothermia

Case Studies1 August 1966Prolonged Spontaneous HypothermiaReport of a Case Associated with Chronic Pancreatitis and a Pemphigoid EruptionGADIEL M. SMITH, M.D., F.A.C.P.GADIEL M. SMITH, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-65-2-316 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThere are three principal types of human hypothermia. They are: [1] accidental—usually due to prolonged exposure to low environmental temperature; [2] induced—used as a therapeutic measure in various medical and surgical situations; and [3] spontaneous or pathologic—a manifestation of a disease state. Although the first two categories are not uncommon and have been well studied, the third is rare.Spontaneous hypothermia is usually associated with severe hypothyroidism or myxedema coma (1). A case unrelated to hypothyroidism will be reported and discussed.CASE REPORTA 68-year-old Negro male was first admitted to the East Orange Veterans Administration Hospital on November 25,...