Chapter 74 Thermal disorders
Body temperature is normally very tightly controlled by a balance between heat production and heat loss, through a complex feedback mechanism involving the thermoregulatory centre in the hypothalamus. In the intensive care unit (ICU), fever (pyrexia) is usually due to resetting of the thermoregulatory set-point at a higher level by activation of heat-conserving mechanisms, whereas hyperthermia is due to failure of effector mechanisms to maintain body temperature at the normal set-point.
THERMOREGULATION
The three major components of the thermoregulatory system are:
Humoral mediators from the circulation act to alter temperature primarily via the organum vasculosum of the lamina terminalis (OVLT), an area of fenestrated capillaries in the hypothalamus that permits cytokine access to neuronal receptors. Cytokines appear to be the endogenous pyrogens, with interleukin-6 (IL-6) and prostaglandin-E2 (PGE2) being a final common pathway. In addition to elevating body temperature, several cytokines also reduce the thermoregulatory set-point, and are known as endogenous cryogens.1
FEVER IN THE ICU
Fever is defined by a regulated hyperthermia, that is, it is a regulated elevation in the preoptic set-point temperature. Endogenous pyrogens as well as other mediators inhibit warm-sensitive neurones that normally facilitate heat loss and suppress heat production. This elevates the set-point temperature for all thermoregulatory responses and activates cold defences such as vasoconstriction and shivering, which decrease heat loss and increase metabolic heat production respectively. The set-point temperature returns to normal when pyrogen concentrations decrease, triggering heat loss by vasodilatation and sweating.2
Fever may reflect a wide variety of pathological processes including infection, inflammation, trauma, malignancy and connective tissue diseases (Table 74.1), necessitating a systematic and comprehensive diagnostic approach.3 It is often assumed that a patient presenting with a fever should be treated, regardless of the presence or absence of other symptoms. However, the evidence that anti-fever treatments lead to an improvement in morbidity or mortality, or even patient comfort, is lacking.4
System | Infectious aetiology | Non-infectious aetiology |
---|---|---|
Cardiovascular | Endocarditis | Myocardial infarction |
Catheter-related infection | Deep-vein thrombosis | |
Pacemaker infection | Pericarditis | |
Respiratory | Pneumonia | Atelectasis |
Empyema | Chemical pneumonitis | |
Sinusitis | Pulmonary emboli | |
Alimentary | Abdominal abscess | Inflammatory bowel disease |
Biliary infection | Acalculous cholecystitis | |
Peritonitis | Pancreatitis | |
Diverticulitis | Ischaemic colitis | |
Viral hepatitis | Non-viral hepatitis | |
Antibiotic-related colitis | Gastrointestinal haemorrhage | |
Renal | Pyelonephritis | |
Urinary tract infection | ||
Central nervous | Meningitis | Cerebral haemorrhage/infarct |
Encephalitis | Seizures | |
Rheumatological | Septic arthritis | Connective tissue disease |
Osteomyelitis | ||
Gout | Vasculitis | |
Endocrine | Adrenocortical insufficiency | |
Alcohol and drug withdrawal | ||
Hyperthyroidism | ||
Skin/soft tissue | Cellulitis | Burns |
Decubitus ulcer | Intramuscular injections | |
Wound infections | ||
Haematoma | ||
Other | Parotitis | Drug fever |
Pharyngitis | Transfusion reaction | |
Otitis media | Neoplasms |
The development of fever in response to infection may be a protective adaptive response, and appears to be a phylogenetically preserved evolutionary response because of its survival value.5 In mammalian models, increasing body temperature results in enhanced resistance to infection. In humans, retrospective clinical trials have shown a positive correlation between maximum temperature on the day of bacteraemia and increased survival in patients with Gram-negative bacteraemia and spontaneous bacterial peritonitis.6 Also, septic patients with hypothermia have a poorer outcome than those who develop fever, although this causality is less clear. Both local and systemic hyperthermia has been used to facilitate cancer treatment. The protective effects of fever result from increased immune and cytokine functions.7–10
Temperature elevation has been shown to enhance:
In addition, elevated temperatures inhibit some pathogens, such as Streptococcus pneumoniae.11
Moderate fever is a common occurrence in ICU patients, but approximately half of these are non-infectious in origin.12–14 The presence of fever frequently results in the performance of diagnostic tests and exposes the patient to unnecessary invasive procedures and inappropriate use of antibiotics.15
Whilst very high fevers (> 40°C) are dangerous, it is less clear whether moderate elevation of body temperature is detrimental and, indeed, may be protective.4 Moreover, artificially lowering the temperature of a febrile patient may mask the signs of infection and make diagnosis and monitoring more difficult. Any decision to adopt anti-fever measures, physical or pharmacological, must take into consideration the variable response by this patient population. Antipyretics may be ineffective.The usual concern about external cooling measures inducing peripheral vasoconstriction, reducing heat loss and making the pyrexia worse by shivering and hypermetabolism, may not be observed in sedated ICU patients.16 The most likely cause for this response is the drugs used to maintain sedation.17,18
Pyrexia is associated with a number of deleterious physiological effects. Cardiac output, oxygen consumption, carbon dioxide production and energy expenditure are all increased, particularly in the presence of shivering. Oxygen consumption is increased on average by 10%/°C.2 These changes are poorly tolerated by patients with limited cardiorespiratory reserve, and this group of patients would probably derive benefit from cooling measures. Other patient groups that require special consideration include those with immunosuppression, prosthetic implants and acute brain injury. Recent trials of therapeutic moderate hypothermia and traumatic brain injury indicate that hypothermia is a complicated treatment that is likely to benefit only a subgroup of patients with traumatic brain injury.19–21
HEAT STROKE
Exertional heat stroke is a consequence of prolonged, intense exercise in warm humid environments, often seen in athletes and military recruits. Classic heat stroke is commonly seen in sedentary, elderly patients with underlying illnesses during heat waves. Factors predisposing to heat stroke are listed in Table 74.2. About 80% of heat stroke deaths occur in people aged 50 years and older, because of the diminished ability of the older body to compensate for increased core temperatures. Heat stroke is estimated to be the cause of approximately 1700 deaths each year in the USA.22 The European heat wave of 2003 was responsible for > 14 000 excess deaths within 2 weeks in France alone, of which a third were attributed to heat stroke, hyperthermia or dehydration.23,24 A high mortality rate of > 62% was reported for this cohort, which is higher than that for leading killers in ICUs such as acute respiratory distress syndrome (ARDS) and septic shock.25 Furthermore, there is a late mortality contributed by survivors who have sustained neurological injury. A study of former heat stroke patients suggests that susceptible individuals have a poorer physiological response to heat stress in terms of core temperature, heart rate and sweat response.
Age | Elderly |
Environmental | High ambient temperature and humidity |
Heat waves | |
Poor ventilation | |
Behavioural | Lack of acclimatisation |
Salt and water deprivation | |
Obesity | |
Underlying conditions | Infection/fever |
Diabetes | |
Malnutrition | |
Alcoholism | |
Hyperthyroidism | |
Impaired sweat production | |
Healed burns | |
Ectodermal dysplasia | |
Impaired sweating | |
Cardiovascular disease | |
Fatigue | |
Potassium deficiency | |
Drugs | Anticholinergics |
Antiparkinsonians | |
Antihistamines | |
Butyrophenones | |
Phenothiazines | |
Tricyclics | |
Diuretics | |
Sympathomimetics |
PATHOGENESIS
The pathogenesis of multiple organ failure in heat stroke is complex. Although direct cellular damage from increased temperature constitutes the initiating insult,26 the precise sequence of injury and responsible mediators are poorly understood. At the cellular level, thermal injury results in increased membrane permeability, which in turn stimulates membrane enzymes such as Na+K+-ATPase to maintain membrane integrity. This ATP-consuming enzyme activity is also responsible for nerve impulse conduction, which ismarkedly curtailed when ATP is depleted. This results in tissue oedema, reduced oxygen extraction and neuronal injury. High temperatures ameliorate ATP synthesis leading to fatigue.
Recent evidence suggests that the pathways for tissue injury in heat stroke share many features with that of sepsis, endotoxaemia and systemic inflammation. Increased levels of circulating endotoxin and cytokines have been identified in patients with heat stroke.27,28 The use of anti-endotoxin antibodies in primate models of heat stroke suggests that endotoxin at least in part mediates the tissue injury associated with hyperthermia. There was also a significant correlation between plasma IL-6 concentration and the severity of heat stroke. Since this cytokine is known to modulate the hypothalamic set-point, the ramifications of such a response in an already hyperthermic patient are obvious.
Activation of coagulation factors29 and release of endothelin and adhesion molecules30,31 from activated or injured endothelium have also been demonstrated in heat stroke. These recent observations lead to the speculation that certain mediators that are implicated in the pathogenesis of acute organ injury are also elevated in heat stress, but become intense when heat stroke develops and are not normalised upon cooling.
CLINICAL PRESENTATION
Dehydration follows excessive insensible losses although sweating is generally absent in the terminal stages of classic heat stroke, leaving a hot, dry skin. Hypovolaemia is a consequence of dehydration and fluid redistribution, and results in reduced organ perfusion. A severe metabolic (lactic) acidosis is present. The major biochemical abnormalities include hyperglycaemia, hypophosphataemia, and raised serum enzymes and acute phase proteins (Table 74.3). Haematological findings include leukocytosis, thrombocytopenia, and activation of coagulation and fibrinolysis.
Classic heat stroke | Exertional heat stoke | |
---|---|---|
Arterial gases | Mixed respiratory alkalosis | Severe metabolic acidosis |
Serum electrolytes | Na+, Mg2+, Ca2+ are usually normal | HyperkalaemiaHypocalcaemia |
Hypophosphataemia | Hyperphosphataemia | |
Blood glucose | Hyperglycaemia | Hypoglycaemia |
Creatinine kinase | Moderately increased | Markedly increased |
Hepatic enzymes | Markedly increased | Moderately increased |
Acute phase proteins | Markedly increased | Moderately increased |
Exertional heat stroke differs slightly in that additional findings include rhabdomyolysis and acute renal failure that is associated with hyperkalaemia, hyperphosphataemia and hypocalcaemia (Table 74.3).
MANAGEMENT
Evaporation is considerably more effective. Pharmacological treatment with antipyretic agents, or dantrolene,32 is ineffective. Prevention of vasoconstriction and shivering by overcooling is important because of the danger of subsequent rebound hyperthermia. Core and skin temperature monitoring is useful, but measurement of rectal temperature should be avoided because it lags considerably during cooling. Cooling can be stopped when core temperature reaches below 39°C. However, despite cooling, about 25% of patients experience failure of one or more organ systems.
OUTCOME
The largest study reported of heat stroke patients in intensive care suggests an alarmingly high mortality of > 60%,23 although this diminishes substantially with early recognition and aggressive treatment. The incidence of permanent neurological deficit remains at 7–15%. Variables associated independently with reduced hospital survival include:
DRUG-INDUCED HYPERTHERMIAS
The numerous causes of hyperthermia are listed in Table 74.4. This section will review the relatively common causes of drug-induced hyperthermias, including malignant hyperthermia, neuroleptic malignant syndrome, and the sympathomimetic and anticholinergic syndromes.
Disorders of excessive heat production | Exertional hyperthermia |
Heat stroke (exertional) | |
Malignant hyperthermia | |
Neuroleptic malignant syndrome | |
Lethal catatonia | |
Thyrotoxicosis | |
Phaeochromocytoma | |
Salicylate intoxication | |
Sympathomimetic drug abuse | |
Delirium tremens | |
Seizures | |
Tetanus | |
Disorders of diminished heat dissipation | Heat stroke (classic) |
Dehydration | |
Autonomic dysfunction | |
Anticholinergic poisoning | |
Neuroleptic malignant syndrome | |
Disorders of hypothalamic function | Cerebrovascular accidents |
Encephalitis | |
Trauma | |
Granulomatous diseases | |
Neuroleptic malignant syndrome |
MALIGNANT HYPERTHERMIA
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