Thermoregulation in the ICU MS.pdf - SASSiT

MGL Spruyt
Dept of Critical Care
University of the Free State
Thermoregulation in the ICU
Physiology of thermoregulation
Heat gain:
continuous metabolic activity
$ Physical activity
$ Shivering
$ Environment
Heat loss:
$ Conduction
$ Convection
$ Radiation
$ Evaporation
Temperature regulation
Peripheral cutaneous thermoreceptors
Lateral spinothalamic tract
anterior hypothalamus - central integrative area - directs thermoregulatory effectors.
Anterior hypothalamus is the heat loss centre
Posterior hypothalamus is the heat maintenance centre.
Together they establish the “set point” for body temperature.
Measuring body temperatures
Esophageal temperature:
$ measured at level of heart
$ closest to mixed venous blood
$ incorrectly placed probes give inaccurate measurements
Nasopharyngeal
$ gives an estimate of hypothalamic temperature
$ inaccurate with uncuffed ET tube
$ may cause nasopharyngeal trauma
Tympanic membrane
$ closely approximates hypothalamic temperature
Bladder temperature
$ accurate method of temperature measurement

$ inaccuracies during abdominal surgery
Rectal temperature
$ affected by cool blood returning from lower extremities, insulation by faeces and heat
producing bowel organisms.
Oral temperature
$ poorly reflects core temperature
$ 0,3 - 0,6C below rectal temperature
Axilla
$ convenient
$ very inaccurate
Skin temperature
$ inaccurate
Fever vs Hyperthermia
Fever
Definition: State of increased core temperature. The Society of Critical Care Medicine defines
fever in ICU as temperature >38,3 C
Febrile response (of which fever is a component):
complex physiological response to disease consisting of
$ cytokine-mediated increase of core temperature set point.
$ generation of acute phase reactions
$ activation of physiological, endocrinological and immunological systems.
Hyperthermia
Unregulated increase in temperature - pyroxenic cytokines are not involved in this process.
$ standard antipyretics are ineffective
$ failure of thermoregulatory homeostasis
$ uncontrolled heat production
$ inadequate heat loss
defective hypothalamic thermoregulation
Hasday and Garrison CID 2000;31 (Suppl 5)

Significance of fever
Benefits:
Fever is an adaptive response to help rid the host of invading pathogens.
Increased temperature enhances the parameters of immune function:
• Antibody production
• T-cell activity
• Production of cytokines
• macrophage function
• Some pathogens (eg S pneumoniae) are inhibited by febrile temperatures
Increased body temperature is associated with improved outcome from infectious disease.
• a positive correlation has been found between the maximum temperature on the day of
bacteraemia and survival (Bryant)
• fever associated with improved survival in patients with spontaneous bacterial peritonitis,
polymicrobial sepsis, E coli bacteraemia and P aeruginosa sepsis.
• conversely, retrospective studies have shown that human survival from serious infections is
reduced in the face of hypothermia (Tc41°C are usually
due to noninfectious causes. Hypothermia, if associated with bacteraemia, signifies a poor
prognosis.
! Frequency
Most patients have remittent or intermittent fever that, when due to infections usually follow a
diurnal
variation.
! Intermittent (septic, quotidian) fever with wide fluctuations may be due to localised
pyogenic infections and bacterial endocarditis, presenting with chills and
leukocytosis.
! Quotidian (daily spike), tertian(every third day) or quartan (every fourth day)
commonly with leukopaenia, may suggest malaria.
! A double quotidian pattern may be helpful in the diagnosis of salmonellosis, miliary
tuberculosis, double malaria infections, and Neisseria endocarditis.
! intermittent hectic (Charcot’s) fever (sporadic episodes) is frequently seen in
cholangitis, usually associated with cholelithiasis, jaundice, leukocytosis and toxic
signs.
! Sustained (continuous) fever may be seen in patients with gram-negative pneumonia
or CNS damage.
! The time points in the course of illness may provide diagnostic clues.
! Pulse/temperature relationship
Relative tachycardia (pulse increased out of proportion to temperature) may point to a toxinmediated
fever (eg gas gangrene) or non-infectious causes.
Relative bradycardia is an indication of legionnaires disease or (in the presence of normal chest X-
rays) drug fever.

! Fever defervescence
Viral infections tend to cause a slow defervescence of fever, while bacterial infections show a
prompt response to appropriate treatment. However, different infections may respond differently
to treament
Post-operative temperature
72% of fevers within 48hrs after surgery are non-infectious. (Garibaldi RA, Infect Contr 6:273,1985)
Pulmonary atelectasis has classically been described as the cause of early potoperative fever, but
more recent evidence has failed to demonstrate an association between atelectasis and body
temperature in the absence of pulmonary infection. (Engoren M. Chest 1995;107:81 - 4) A
regulated elevation in the core temperature setpoint occurs normally after surgery. The elevation
is associated with the extent and duration of surgery, and with a cytokine response, suggesting that
early postoperative fever is a manifestation of perioperative stress and tissue injury.
Frank et al found that approximately 25% of patient post-operatively had a core temperature
38,5°C, suggesting that the traditional definition of post-operative fever of 38,5°C is too
stringent.
Drug fever
Drug fever should be considered in patients with an otherwise unexplained fever, especially if they
are receiving -lactam antibiotics. Typically, drug fever presents with high spiking temperature and
shaking chills, and may be associated with leukocytosis and eosinophilia.
Fever in neurosurgical patients
The incidence of pyrexia is increased in patients with a Glasgow Coma scale of 2X). Fever in the brain injured
patient exacerbates ischaemic neuronal damage and physiological dysfunction. Pyrexia affects the
acutely injured brain through several mechanisms:
! increased glutamate release, Oxygen free radical production
! Augments permeability of the blood brain barrier, increasing edme
! increases cyto-skeletal protein degradation
Fever in HIV infected patients
Fever is common in HIV infected patients. The initial acute infection is characterised by a
mononucleosis-like syndrome with fever. An acute febrile illness of 2 -3 weeks duration occurs 2-4
weeks after seroconversion in 50 - 70% of HIV-infected patients. The diagnosis may be established
by demonstrating a high viral load combined with negative or indeterminate HIV serology followed
by seroconversion. Approximately 20% of AIDS patients receiving trimethoprim-sulfamethoxazole
develop fever, usually accompanied by a typical rash or pruritus. Fever in the subsequent course of
HIV infection usually represents superimposed complications of late-stage disease.
Management of fever
To treat or not: benefit vs risk
Fever is a host defence mechanism. Temperature in the range of usual fever renders host defences
more active and many pathogens more susceptible to defences. Temperature is also an important
physical sign in the monitoring of the response to treatment. Therefore in is recommended that
febrile episodes should not be routinely treated with anti-pyretic therapy; relative benefits and
risks of treatment should be evaluated in every case.
Fever should be treated in patients with acute brain insults, with limited cardiorespiratory reserve,
and in patients in whom the temperature increases above 40°C.
Physical cooling
Hypothermia blankets, etc have been found to be no more effective than antipyretics. They may be

associated with large temperature fluctuations and rebound hyperthermia. Due to the higher
setpoint, the patient already responds as if to a cold environment. External cooling may lead to
increased hypermetabolism and persistent fever (Marik PE; Chest 117:3; March 2000), and increased
oxygen consumption. It is also associated with a significant increase in adrenaline and noradrenaline
levels. Lenhardt et al suggest that a more rational strategy for treating fevers unresponsive to
antipyretic drugs is to promote heat loss by warming selected skin surfaces, thereby reducing the
vasoconstriction and shivering thresholds associated with the elevated hypothalamic thermal set
point. (Lenhardt R et al Acta Anaesthesiol Scan Suppl 1996;109)
Antipyretics
Antipyretics
• do not lower temperature unless fever is present (ie elevated set point)
• do not affect circadian rhythm of temperature.
Most antipyretic drugs work by inhibiting the enzyme cyclooxygenase and reducing the levels of PGE 2
within the hypothalamus. Other mechanisms of action have been suggested, including the drugs’
ability to reduce proinflammatory mediators, enhance anti-inflammatory signals at sites of injury, or
boost antipyretic messages within the brain. Antipyretics in common use today include paracetamol,
aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).
Cyclooxygenase
The major mechanism of action of aspirin and other antipyretics involves lowering PGE 2
by direct
inhibition of COX enzyme activity. Sodium salicylate, aspirin’s major metabolite, exhibits similar
antipyretic and anti-inflammatory properties as aspirin but only weak inhibition of COX-1 and COX-2
in vitro.
NSAIDs are also capable of reducing PGE 2
production by down-regulating the expression of COX
enzymes. Salicylates and some other NSAIDs like ibuprofen also work by preventing NF-B
translocation in endothelial cells and leukocytes. Indomethacin and therapeutic doses of
paracetamol, however, do not appear to affect NF-B.
Noncyclooxygenase targets for antipyretics
Some of the clinically useful actions of antipyretics may be COX independent, and with antiinflammatory
effects seen only with doses much higher than required to suppress COX activity. For
example, the also suppress tissue inflammation through diminished leukocyte-endothelial cell
interactions, reduced pyrogenic cytokine production or enhanced expression of anti-inflammatory
molecules.
Mechanisms such as boosting the activity of endogenous antipyretic messengers have been described.
Associated with the febrile response is the activation of multiple endogenous antipyretic systems
that serve to suppress the magnitude or duration of fever. These include neuroactive substances of
neural and humoral origin, eg glucocorticoids, vasopressin and melanocortins. It is thought that
endogenous antipyretic systems protect the host against the destructive effects of unchecked fever.
The endogenous antipyretic substances participate in the antipyretic mechanism of salicylates and
related NSAIDs, but not paracetamol.
NSAIDs, particularly those with substantial COX -1 inhibition, are potentially damaging to the kidneys
and gastro-intestinal tract.
Under conditions of decreased renal perfusion, the production of renal PGs serves as an important
compensatory mechanism.
Renal effects of NSAIDs are based on their pharmacologic mechanism of action. These effects are
relatively mild and rare in healthy individuals but can be serious in patients whose renal function is
prostaglandin-dependent. Patients with contracted effective intravascular fluid volume are more
likely to experience NSAID-related changes in renal function.

Acute renal failure with NSAID therapy is mediated haemodynamically as a result of decreased renal
perfusion after inhibition of prostacyclin synthesis. Renal effects of specific COX-2 inhibitors seem to
be similar to those seen with traditional NSAIDs.
Very rare adverse renal effects of NSAID therapy include nephritic syndrome and papillary necrosis.
Acute interstitial nephritis can develop at any time during therapy and is usually combined with
minimal-change glomerulonephritis. The adverse renal effects of NSAIDs have been observed to occur
more frequently under physiologic conditions that have been previously correlated with increased
dependence of renal function on Pgs.
Certain antipyretic drugs may cause coronary vasoconstriction in patients with coronary artery
disease. Indomethacin has been shown to cause significant increases in mean arterial pressure,
coronary vascular resistance and myocardial arteriovenous oxygen difference. Therefore, myocardial
oxygen demand increases in the face of a decrease in coronary blood flow after administration of
indomethacin. (Friedman et al; NEJM 1981;305)
Hyperthermia
Heat syndromes:
! Heat cramps to heat stroke.
Heat stroke is defined clinically as a core body temperature that rises above 40°C and is
accompanied by hot, dry skin and central nervous system abnormalities such as delirium, convulsions
or coma. Heat stroke develops as a result of exposure to high environmental temperature or from
strenuous exercise. Bouchama et al (NEJM 346:25; 2002) suggest an alternative definition: heat
stroke is a form of hyperthermia associated with a systemic inflammatory response leading to a
syndrome of multiorgan dysfunction in which encephalopathy predominates.

Endothelial-cell injury and diffuse microvascular thrombosis are prominent features of heat stroke.
The most serious complications include encephalopathy, rhabdomyolysis, acute renal failure, ARDS,
myocardial injury, hepatocellular injury, intestinal ischaemia or infarction, pancreatic injury and
haemorrhagic complication, especially disseminated intravascular coagulation with pronounced
thrombocytopenia.

Treatment of heatstroke
The two main therapeutic objectives in heat stroke are immediate cooling and support of organsystem
function. Therapeutic cooling techniques are aimed at accelerating the transfer of heat from
the skin to the environment without compromising skin perfusion. To overcome the cutaneous
vasoconstriction and shivering resulting form rapid cooling of the skin, the patient may be vigorously
massaged, sprayed with tepid water (40°C) or exposed to hot moving air. Antipyretic agents and
drugs that accelerate cooling are not useful in the treatment of heatstroke.
Cooling techniques
Conductive cooling
External
Coldwater immersion
cold packs or ice slush
Use of cooling blankets.
Internal
Iced gastric lavage
Iced peritoneal lavage
Evaporative or convective cooling
Fanning the undressed patient at room
temperature (20°C - 22°C)
Wetting the body surface during
continuous fanning
! Neuroleptic Malignant syndrome
NMS is a drug-induced disorder presenting with rigidity, dyskinesia, rhabdomyolysis, hyperthermia,
changes in mental status, and autonomic nervous system instability. It is uncommon but lifethreatening.
The disorder is associated particularly with the use of antipsychotic, neuroleptic drugs.
Treatment consists of immediate discontinuation of the suspected medication. Supportive care
includes iv hydration, and monitoring of cardiac rhythm, respiratory status and renal perfusion.
Pharmacologic therapy is aimed at increasing dopaminergic activity with bromocriptine and
dantrolene sodium.
! Malignant hyperthermia.
MH is a life-threatening disorder occurring in susceptible patients after receiving inhalation
anaesthetics (eg halothane) and succinylcholine. It presents with fever 40°C, muscle rigidity,
tachycardia and tachypnoea. It affects multiple systems in the body and can lead to disseminated
intravascular coagulation and precipitate seizures if not diagnosed and treated.
Treatment
Anaesthesia is discontinued and the patient hyperventilated with 100% oxygen. Dantrolene sodium is
given intravenously. Signs and symptoms can be manifested up to 12 hours after anaesthesia with
causative agents.

Medications for treatment of
hyperthermia
Convulsions
Diazepam 5 - 20 mg iv
Mannitol 1mg/kg to reduce cerebral edema
Phenobarbital 130 - 260mg initially iv
Hypocalcaemia
no treatment unless cardiac symptoms
present
Hypokalaemia
Replace deficits carefully
Myoglobinuria
Mannitol 12,5g initially iv, then 12,5g/litre
crystalloid.
Maintain urine output at 50ml/h
Alkalinise urine with bicarbonate
Dialysis if indicated

Hypothermia
Medical illness
Secondary hypothermia results when a disease state interferes with thermoregulation. Hypothermia
may be associated with medical conditions such as sepsis, chronic heart failure, diabetes mellitus
and hypothyroidism.
Accidental
! peri-operative
! Exposure
! Trauma
Therapeutic.
Hypothermia improves survival from many insults. Studies have suggested benefit of induced
hypothermia applied in the ICU in traumatic brain injury and ARDS, and possibly anoxic brain injury.
Potential applications in the ICU include:
Neurosurgery
! traumatic brain injury
! Cerebral aneurysm
Neurology
! Anoxic brain injury
! cerebral haemorrhage
! Carbon Monoxide poisoning
! status epilepticus
! Air Embolism Syndrome
General Surgery
! burns
Respiratory system
! Acute respiratory distress syndrome
! Asthma
Cardiology
! refractory tachyarrhythmias
Other
! eclampsia
! Sepsis syndrome
The method of achieving reduction in body temperature, whether forced or regulated, may have a
profound effect on the therapeutic efficacy of hypothermia. Regulated hypothermia seems to be
the best means of achieving therapeutic benefit. Forcing body temperature below the set point
temperature results in an immediate response to increase heat production and reduce heat loss. If
body temperature were reduced by a regulated mechanism, the onset of the regulated hypothermic
response would be characterised by peripheral vasodilatation, sweating and suppression of heat gain
thermoeffectors. Activation of physiological systems such as tachycardia, tachypnoea,
corticosteroid and adrenaline release would be expected to be minimal during regulated
hypothermia
Classification:
! mild 32C - 35C
! moderate 28C - 32C
! severe < 28C
Committee on Trauma of the American College of Surgeons
!

Consequences of hypothermia
Mild hypothermia
• tachypnoea
• vasoconstriction
• tachycardia
• ataxia
• dysarthria
• loss of fine motor coordination
• lethargy
• confusion
• shivering
Moderate hypothermia
• shivering stops
• delirium
• reflexes slowed
• level of consciousness diminishes
• bradycardia
• J wavers on ECG
• Cold diuresis
Severe hypothermia
• unresponsiveness or coma
• hypotension very cold skin pulmonary edema
• acidaemia
• may appear dead
• ventricular fibrillation
• loss of reflexes
Hypothermia-induced complications
Myocardial Ischaemia
High risk patients with only 1,3°C core hypothermia are three times as likely to experience adverse
myocardial outcomes. Hypothermia causes hypertension in elderly patients and those at high risk
for cardiac complications, and is associated with a threefold increase in plasma noradrenaline
concentration which may increase cardiac irritability and the development of ventricular
arrythmias. (Frank et al JAMA 1997/ClinSci 1996; Anesthesiology 1995)
Coagulopathy
Mild hypothermia increases blood loss. (Schmied et al Lancet1996) Just 1,6°C core temperature loss
may increase blood loss by 500ml (30%). Hemostatic benefits are achieved by maintaining
intraoperative normothermia.
Three mechanisms contribute to temperature-related coagulation disorders: platelet function,
clotting factor enzyme function, and fibrinolytic activity. In hypothermic coagulopathy standard
coagulation tests, including the prothrombin time and the partial thromboplastin times, remain
normal because the tests are performed at 37°C regardless of what the patient’s temperature is.

Fibrinolysis appears to remain normal during mild hypothermia but is significantly increased during
hyperthermia. Thromboelastography suggests that hypothermia impairs clot formation rather than
facilitating clot degeneration.
Wound infection and Healing.
Hypothermia impairs neutrophil function directly, or indirectly by triggering subcutaneous
vasoconstriction and subsequent tissue hypoxia. 1,9°C core hypothermia triples the incidence of
surgical wound infection after colon resection. Hypothermia also increases the duration hospital
stay by 20% and aggravates postoperative protein wasting.
Pharmacokinetics and pharmacodynamics.
• The duration of action of muscle relaxants are generally prolonged in the presence of
hypothermia.
• The tissue solubility of volatile anaesthetics increases with hypothermia, so that body
anaesthetic content is increased at subnormal temperatures. This does not alter
anaesthetic potency but may slow recovery from anaesthesia because larger amounts of
anaesthetic eventually need to be exhaled.
Recovery duration and thermal discomfort.
• Mild hypothermia produces marked postoperative thermal discomfort and may delay
discharge of adult patient from the postanaesthesia care unit.
Minor consequences
• mild hypokalaemia
• increased cardiotoxicity of bupivacaine.
• Sufficient vasoconstriction resulting partly from hypothermia can obliterate the pulse
oximeter signal.
Treatment of hypothermia
Accidental hypothermia
Prognosis
Patients found in a hypothermic situation should not be pronounced dead until reassessment after
rewarming to at least 33°C.
Mortality among hypothermic patients is variable (12 - 80%), and depends on the cause of
hypothermia, the patient’s age and background, the delay before treatment, and probably
sometimes the rewarming modality.
Severity factors include old age, low blood pressure, low blood bicarbonate level, high SAPS II score,
need for mechanical ventilation or vasoactive drugs, discovery of the patient at home, hypothermia
not due to acute intoxication, and long delay before rewarming.
The baseline temperature is not a factor of poor prognosis according to most studies. In trauma
cases, however, retrospective studies have found an association between higher mortality and
degree of hypothermia. Jurkovich et al (J Trauma 1987) found that no trauma patient whose core
temperature fell below 32°C survived. The rewarming rate and the delay after the accident appear
to be most important prognostic factors. In-hospital rewarming requiring >12h is a grave prognostic
sign. Major hyperkalaemia (>10mmol/l) is a factor of poor prognosis only in asphyxiated avalanche
victims.
Treatment
Cardiopulmonary resuscitation should be instituted if no pulse is present.
• many arrhythmias convert spontaneously upon rewarming, and aggressive therapy of minor
arrhythmias is not warranted. Transient ventricular arrhythmias, bradycardia or atrial
arrhythmias should be ignored.
• Defibrillate at 2 J/kg if the patient is in ventricular fibrillation or ventricular tachycardia,
and promptly administer amiodarone. Success rates of defibrillation are low if the core

temperature is less than 32°C.
• If defibrillation fails, attempts should be repeated after every 1°C rise in body temperature.
• Rapid fluid resuscitation usually is necessary because cardiovascular efficiency improves
with crystalloid administration.
• Hypotension is treated by volume replacement and rewarming. Vasopressors should be
avoided because they have little effect on vasoconstriction secondary to hypothermia and
can precipitate ventricular fibrillation.
The cornerstone of treatment is rewarming the patient.
Passive rewarming
• Insulating or reflective blanket
• Raise ambient temperature
• keep patient dry
Active external rewarming: External heat applied to the patient’s skin in a noninvasive manner.
• Immersion in water bath at 40°C (makes monitoring and resuscitation difficult.
• Radiant heat sources; heated blankets and heating pads.
• Forced -air rewarming can rewarm as fast as 2,4°C/h (eg convective warming covers)
Active core rewarming
• humidify inspired air
• warm intravenous fluids and blood products. These methods are used as an adjunct to other
methods.
• Heated gastric and colonic lavage.
• pleural lavage
• peritoneal lavage
• mediastinal or closed thoracic lavage: These methods may induce ventricular fibrillation and
should only be used if cardiopulmonary bypass is immediately available.
Extracorporal blood rewarming
• Haemodialysis
• Continuous arteriovenous rewarming (CAVR)
• Venovenous rewarming
• Cardiopulmonary bypass. Standard cardiopulmonary bypass requires not only specialised
equipment and staff, but also mandated systemic anticoagulation and is not suitable for use
in managing hypothermia in trauma victims.
Conclusion:
Both fever and hypothermia have benefits and detrimental effects. These should be weighed in the
decision to treat; the etiology and pathophysiology should lead decisions on how to treat. Both
hyper- and hypothermia may also have therapeutic uses.
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