3. GUIDED BY:
• DR.NAVIN SHAH
• DR.RAKESH SHAH
• DR.KRUTI SHAH
• DR.AMIT MAHAJAN
• DR.PRACHUR
• DR.ANANTH
• DR.DIXIT SHAH
• DR.DEEPANKAR
4. CONTENT
• INTRODUCTION
• FEVER
• HYPERPYREXIA
• HYPERTHERMIA
• PATHOGENESIS OF FEVER
• APPROACHTO THE PATIENT
• ANTIPYRETIC DRUG
• FEVER OF UNKNOWN ORIGIN
• HYPOTHERMIA
5. INTRODUCTION
• Body temperature is controlled by the hypothalamus.
• Neurons in both the preoptic anterior hypothalamus and the posterior
hypothalamus receive two kinds of signals:
• one from peripheral nerves that transmit information from warmth/cold
receptors in the skin
• and the other from the temperature of the blood bathing the region.
• These two types of signals are integrated by the thermoregulatory center
of the hypothalamus to maintain normal temperature.
• In a neutral temperature environment, the metabolic rate of humans
produces more heat than is necessary to maintain the core body
temperature at 37°C.
6. • A normal body temperature is ordinarily maintained, despite
environmental variations, because the hypothalamic
thermoregulatory center balances the excess heat production derived
from metabolic activity in muscle and the liver with heat dissipation
from the skin and lungs.
• According to studies of healthy individuals 18–40 years of age, the
mean oral temperature is 36.8° ± 0.4°C (98.2° ± 0.7°F), with low levels
at 6 A.M. and higher levels at 4–6 P.M.
• The maximum normal oral temperature is 37.2°C (98.9°F) at 6 A.M.
and 37.7°C (99.9°F) at 4 P.M.; these values define the 99th percentile
for healthy individuals.
• In light of these studies, an A.M. temperature of >37.2°C (>98.9°F) or
a P.M. temperature of >37.7°C (>99.9°F) would define a fever.
7. • In women who menstruate, the A.M. temperature is generally lower
in the 2 weeks before ovulation; it then rises by ~0.6°C (1°F) with
ovulation and remains at that level until menses occur. Body
temperature can be elevated in the postprandial state. Pregnancy and
endocrinologic dysfunction also affect body temperature.
8. FEVER
• Fever is an elevation of body temperature that exceeds the normal daily
variation and occurs in conjunction with an increase in the hypothalamic
set point (e.g., from 37°C to 39°C).
• This shift of the set point from "normothermic" to febrile levels very
much resembles the resetting of the home thermostat to a higher level
in order to raise the ambient temperature in a room.
• Once the hypothalamic set point is raised, neurons in the vasomotor
center are activated and vasoconstriction commences. The individual
first notices vasoconstriction in the hands and feet. Shunting of blood
away from the periphery to the internal organs essentially decreases
heat loss from the skin, and the person feels cold.
• For most fevers, body temperature increases by 1°–2°C.
9. • Shivering, which increases heat production from the muscles, may
begin at this time; however, shivering is not required if heat
conservation mechanisms raise blood temperature sufficiently.
Nonshivering heat production from the liver also contributes to
increasing core temperature.
• In humans, behavioral adjustments (e.g., putting on more clothing or
bedding) help raise body temperature by decreasing heat loss.
10. • The processes of heat conservation (vasoconstriction) and
heat production (shivering and increased nonshivering
thermogenesis) continue until the temperature of the blood
bathing the hypothalamic neurons matches the new
thermostat setting.
• Once that point is reached, the hypothalamus maintains the
temperature at the febrile level by the same mechanisms of
heat balance that function in the afebrile state.
11. • When the hypothalamic set point is again reset downward (in
response to either a reduction in the concentration of pyrogens or
the use of antipyretics), the processes of heat loss through
vasodilation and sweating are initiated. Loss of heat by sweating and
vasodilation continues until the blood temperature at the
hypothalamic level matches the lower setting. Behavioral changes
(e.g., removal of clothing) facilitate heat loss.
12. HYPERPYREXIA
• A fever of >41.5°C (>106.7°F) is called hyperpyrexia. This
extraordinarily high fever can develop in patients with severe
infections but most commonly occurs in patients with central nervous
system (CNS) hemorrhages. In the preantibiotic era, fever due to a
variety of infectious diseases rarely exceeded 106°F, and there has
been speculation that this natural "thermal ceiling" is mediated by
neuropeptides functioning as central antipyretics.
13. HYPOTHALAMIC FEVER
• In rare cases, the hypothalamic set point is elevated as a result of
local trauma, hemorrhage, tumor, or intrinsic hypothalamic
malfunction. The term hypothalamic fever is sometimes used to
describe elevated temperature caused by abnormal hypothalamic
function. However, most patients with hypothalamic damage have
subnormal, not supranormal, body temperatures.
14. HYPERTHERMIA
• Although most patients with elevated body temperature have fever,
there are circumstances in which elevated temperature represents
not fever but hyperthermia.
• Hyperthermia is characterized by an uncontrolled increase in body
temperature that exceeds the body's ability to lose heat.
• The setting of the hypothalamic thermoregulatory center is
unchanged.
15. • In contrast to fever in infections, hyperthermia does not involve
pyrogenic molecules (see "Pyrogens," below). Exogenous heat
exposure and endogenous heat production are two mechanisms by
which hyperthermia can result in dangerously high internal
temperatures. Excessive heat production can easily cause
hyperthermia despite physiologic and behavioral control of body
temperature. For example, work or exercise in hot environments can
produce heat faster than peripheral mechanisms can lose it
19. Approach to the Patient: Fever or Hyperthermia
Physical Examination
• Attention must be paid to the chronology of events and to other signs and
symptoms preceding the fever. The temperature may be taken orally or
rectally, but the site used should be consistent. Axillary temperatures are
notoriously unreliable. Electronic devices for measuring tympanic membrane
temperatures are reliable and preferred over oral temperature measurements
in patients with pulmonary disease such as acute infection or asthma.
Laboratory Tests
• The workup should include a complete blood count; a differential count
should be performed manually or with an instrument sensitive to the
identification of eosinophils, juvenile or band forms, toxic granulations, and
Döhle bodies, the last three of which are suggestive of bacterial infection.
Neutropenia may be present with some viral infections.
20. • Measurement of circulating cytokines in patients with fever is of little
use since levels of pyrogenic cytokines in the circulation often are
below the detection limit of the assay or do not coincide with the
fever. Although some studies have shown correlations between
circulating IL 6 levels and peak febrile elevations, the most valuable
measurements in patients with fever are C-reactive protein level and
erythrocyte sedimentation rate. These markers of pathologic
processes are particularly helpful in identifying disease in patients
with small elevations in body temperature
21. Fever in Recipients of Anticytokine Therapy
• As of this writing, more than 750,000 patients in the United States are
receiving chronic anticytokine therapy for Crohn's disease, rheumatoid
arthritis, or psoriasis. Does such therapy mask infection by preventing
fever? With the increasing use of anticytokines to reduce the activity of IL-
1, IL-6, IL-12, and TNF, the effect of these agents on the febrile response
must be considered.
• The blocking of cytokine activity has the distinct clinical drawback of
lowering the level of host defenses against both routine bacterial and
opportunistic infections. The opportunistic infections reported in patients
given neutralizing antibodies to TNF- (infliximab or adalimumab) are similar
to those reported in the HIV-1-infected population (e.g., new infection with
or reactivation of Mycobacterium tuberculosis , with dissemination). A
soluble receptor for TNF, etanercept, is also associated with opportunistic
infections but less so than the neutralizing antibodies.
22. • In nearly all reported cases of infection associated with anticytokine
therapy, fever is among the presenting signs. However, the extent to
which the febrile response is reduced in these patients remains
unknown. Fever in a patient who develops an infection during
anticytokine treatment is likely to be due to the direct action of
microbial products on the hypothalamic thermoregulatory center,
with induction of PGE2. For example, blocking the activity of IL-1 or
TNF during experimental endotoxin-induced fever in volunteers does
not affect the febrile response.
23. Fever and Hyperthermia: Treatment
• The Decision to Treat Fever
• Most fevers are associated with self-limited infections, such as common viral
diseases. The use of antipyretics is not contraindicated in these infections:
there is no significant clinical evidence that antipyretics delay the resolution of
viral or bacterial infections, nor is there evidence that fever facilitates recovery
from infection or acts as an adjuvant to the immune system. In fact, peripheral
PGE2 production is a potent immunosuppressant. In short, treatment of fever
and its symptoms does no harm and does not slow the resolution of common
viral and bacterial infections.
24. • However, in bacterial infections, withholding antipyretic therapy can be
helpful in evaluating the effectiveness of a particular antibiotic therapy,
particularly in the absence of cultural identification of the infecting
organism. The routine use of antipyretics can mask an inadequately treated
bacterial infection. Withholding antipyretics in some cases may facilitate
the diagnosis of an unusual febrile disease. For example, the usual times of
peak and trough temperatures may be reversed in typhoid fever and
disseminated tuberculosis. Temperature-pulse dissociation (relative
bradycardia) occurs in typhoid fever, brucellosis, leptospirosis, some drug-
induced fevers, and factitious fever. In newborns, the elderly, patients with
chronic renal failure, and patients taking glucocorticoids, fever may not be
present despite infection, or core temperature may be hypothermic.
Hypothermia is often observed in patients with septic shock.
25. • Some infections have characteristic patterns in which febrile episodes
are separated by intervals of normal temperature. For example,
Plasmodium vivax causes fever every third day, whereas fever occurs
every fourth day with P. malariae. Other relapsing fevers are related
to Borrelia infections, with days of fever followed by a several-day
afebrile period and then a relapse of days of fever. In the Pel-Ebstein
pattern, fever lasting 3–10 days is followed by afebrile periods of 3–10
days; this pattern can be classic for Hodgkin's disease and other
lymphomas. In cyclic neutropenia, fevers occur every 21 days and
accompany the neutropenia. There is no periodicity of fever in
patients with familial Mediterranean fever.
26. • Recurrent fever is documented at some point in most autoimmune
diseases and all autoinflammatory diseases. The autoinflammatory
diseases include adult and juvenile Still's disease, familial Mediterranean
fever, hyper-IgD syndrome, familial cold-induced autoinflammatory
syndrome, neonatal-onset multisystem autoinflammatory disease, Blau
syndrome, Schnitzler syndrome, Muckle-Wells syndrome, and TNF
receptor–associated periodic syndrome. Besides recurrent fevers,
neutrophilia and serosal inflammation characterize these diseases. The
fevers associated with these illnesses are dramatically reduced by blocking
of IL-1 activity. Anticytokines therefore reduce fever in autoimmune and
autoinflammatory diseases. Although fevers in autoinflammatory diseases
are mediated by IL-1, patients also respond to antipyretics
27. Mechanisms of Antipyretic Agents
• The reduction of fever by lowering of the elevated hypothalamic set point
is a direct function of reducing the level of PGE2 in the thermoregulatory
center. The synthesis of PGE2 depends on the constitutively expressed
enzyme cyclooxygenase. The substrate for cyclooxygenase is arachidonic
acid released from the cell membrane, and this release is the rate-limiting
step in the synthesis of PGE2. Therefore, inhibitors of cyclooxygenase are
potent antipyretics. The antipyretic potency of various drugs is directly
correlated with the inhibition of brain cyclooxygenase. Acetaminophen is a
poor cyclooxygenase inhibitor in peripheral tissue and lacks noteworthy
anti-inflammatory activity; in the brain, however, acetaminophen is
oxidized by the p450 cytochrome system, and the oxidized form inhibits
cyclooxygenase activity. Moreover, in the brain, the inhibition of another
enzyme, COX-3, by acetaminophen may account for the antipyretic effect
of this agent. However, COX-3 is not found outside the CNS.
28. • Oral aspirin and acetaminophen are equally effective in reducing fever in
humans. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen
and specific inhibitors of COX-2 are also excellent antipyretics. Chronic,
high-dose therapy with antipyretics such as aspirin or any NSAID does not
reduce normal core body temperature. Thus, PGE2 appears to play no role
in normal thermoregulation.
• As effective antipyretics, glucocorticoids act at two levels. First, similar to
the cyclooxygenase inhibitors, glucocorticoids reduce PGE2 synthesis by
inhibiting the activity of phospholipase A2, which is needed to release
arachidonic acid from the cell membrane. Second, glucocorticoids block
the transcription of the mRNA for the pyrogenic cytokines. Limited
experimental evidence indicates that ibuprofen and COX-2 inhibitors
reduce IL-1-induced IL-6 production and may contribute to the antipyretic
activity of NSAIDs.
29. Regimens for the Treatment of Fever
• The objectives in treating fever are first to reduce the elevated
hypothalamic set point and second to facilitate heat loss. Reducing
fever with antipyretics also reduces systemic symptoms of headache,
myalgias, and arthralgias.
• Oral aspirin and NSAIDs effectively reduce fever but can adversely
affect platelets and the gastrointestinal tract. Therefore,
acetaminophen is preferred to all of these agents as an antipyretic. In
children, acetaminophen must be used because aspirin increases the
risk of Reye's syndrome. If the patient cannot take oral antipyretics,
parenteral preparations of NSAIDs and rectal suppository
preparations of various antipyretics can be used.
30. • Treatment of fever in some patients is highly recommended. Fever
increases the demand for oxygen (i.e., for every increase of 1°C over 37°C,
there is a 13% increase in oxygen consumption) and can aggravate
preexisting cardiac, cerebrovascular, or pulmonary insufficiency. Elevated
temperature can induce mental changes in patients with organic brain
disease. Children with a history of febrile or nonfebrile seizure should be
aggressively treated to reduce fever, although it is unclear what triggers the
febrile seizure and there is no correlation between absolute temperature
elevation and onset of a febrile seizure in susceptible children.
• In hyperpyrexia, the use of cooling blankets facilitates the reduction of
temperature; however, cooling blankets should not be used without oral
antipyretics. In hyperpyretic patients with CNS disease or trauma, reducing
core temperature mitigates the ill effects of high temperature on the brain.
31. Treating Hyperthermia
• A high core temperature in a patient with an appropriate history (e.g.,
environmental heat exposure or treatment with anticholinergic or
neuroleptic drugs, tricyclic antidepressants, succinylcholine, or halothane)
along with appropriate clinical findings (dry skin, hallucinations, delirium,
pupil dilation, muscle rigidity, and/or elevated levels of creatine
phosphokinase) suggests hyperthermia. Attempts to lower the already
normal hypothalamic set point are of little use. Physical cooling with
sponging, fans, cooling blankets, and even ice baths should be initiated
immediately in conjunction with the administration of IV fluids and
appropriate pharmacologic agents (see below). If insufficient cooling is
achieved by external means, internal cooling can be achieved by gastric or
peritoneal lavage with iced saline. In extreme circumstances, hemodialysis
or even cardiopulmonary bypass with cooling of blood may be performed.
32. • Malignant hyperthermia should be treated immediately with cessation of
anesthesia and IV administration of dantrolene sodium. The recommended
dose of dantrolene is 1–2.5 mg/kg given intravenously every 6 h for at least
24–48 h—until oral dantrolene can be administered, if needed.
Procainamide should also be administered to patients with malignant
hyperthermia because of the likelihood of ventricular fibrillation in this
syndrome. Dantrolene at similar doses is indicated in the neuroleptic
malignant syndrome and in drug-induced hyperthermia and may even be
useful in the hyperthermia of the serotonin syndrome and thyrotoxicosis.
The neuroleptic malignant syndrome may also be treated with
bromocriptine, levodopa, amantadine, or nifedipine or by induction of
muscle paralysis with curare and pancuronium. Tricyclic antidepressant
overdose may be treated with physostigmine
33. Fever of unknown origin
• Fever of unknown origin (FUO) was defined by Petersdorf and Beeson
in 1961 as (1) temperatures of >38.3°C (>101°F) on several occasions;
(2) a duration of fever of >3 weeks; and (3) failure to reach a diagnosis
despite 1 week of inpatient investigation. While this classification has
stood for more than 30 years, Durack and Street have proposed a new
system for classification of FUO: (1) classic FUO; (2) nosocomial FUO;
(3) neutropenic FUO; and (4) FUO associated with HIV infection.
34. • Classic FUO corresponds closely to the earlier definition of FUO,
differing only with regard to the prior requirement for 1 week's study
in the hospital. The newer definition is broader, stipulating three
outpatient visits or 3 days in the hospital without elucidation of a
cause or 1 week of "intelligent and invasive" ambulatory
investigation.
• In nosocomial FUO, a temperature of 38.3°C (101°F) develops on
several occasions in a hospitalized patient who is receiving acute care
and in whom infection was not manifest or incubating on admission.
Three days of investigation, including at least 2 days' incubation of
cultures, is the minimum requirement for this diagnosis
35. • Neutropenic FUO is defined as a temperature of 38.3°C (101°F) on
several occasions in a patient whose neutrophil count is <500/L or is
expected to fall to that level in 1–2 days. The diagnosis of neutropenic
FUO is invoked if a specific cause is not identified after 3 days of
investigation, including at least 2 days' incubation of cultures.
• HIV-associated FUO is defined by a temperature of 38.3°C (101°F) on
several occasions over a period of >4 weeks for outpatients or >3 days
for hospitalized patients with HIV infection. This diagnosis is invoked if
appropriate investigation over 3 days, including 2 days' incubation of
cultures, reveals no source.
36.
37.
38. Fever of Unknown Origin: Treatment
• The focus here is on classic FUO. Other modifiers of FUO—neutropenia, HIV infection, a
nosocomial setting—all vastly affect the risk equation and dictate therapy based on the
probability of various causes of fever and on the calculated risks and benefits of a guided
empirical approach. The age and physical state of the patient are factors as well: the frail
elderly patient may merit a trial of empirical therapy earlier than the robust young adult.
• The emphasis in patients with classic FUO is on continued observation and examination,
with the avoidance of "shotgun" empirical therapy. Antibiotic therapy (even that for
tuberculosis) may irrevocably alter the ability to culture fastidious bacteria or
mycobacteria and delineate ultimate cause. However, vital-sign instability or neutropenia
is an indication for empirical therapy with a fluoroquinolone plus piperacillin or the
regimen mentioned above (see "Nosocomial FUO"), for example. Cirrhosis, asplenia,
intercurrent immunosuppressive drug use, or recent exotic travel may all tip the balance
toward earlier empirical anti-infective therapy. If the PPD skin test is positive or if
granulomatous hepatitis or other granulomatous disease is present with anergy (and
sarcoid seems unlikely), then a therapeutic trial with isoniazid and rifampin (and possibly
a third drug) should be undertaken, with treatment usually continued for up to 6 weeks.
A failure of the fever to respond over this period suggests an alternative diagnosis.
39. • The response of rheumatic fever and Still's disease to aspirin and nonsteroidal
anti-inflammatory drugs (NSAIDs) may be dramatic. The effects of glucocorticoids
on temporal arteritis, polymyalgia rheumatica, and granulomatous hepatitis are
equally dramatic. Colchicine is highly effective in preventing attacks of familial
Mediterranean fever but is of little use once an attack is well under way. The
ability of glucocorticoids and NSAIDs to mask fever while permitting the spread of
infection dictates that their use be avoided unless infection has been largely ruled
out and unless inflammatory disease is both probable and debilitating or
threatening.
• When no underlying source of FUO is identified after prolonged observation (>6
months), the prognosis is generally good, however vexing the fever may be to the
patient. Under such circumstances, debilitating symptoms are treated with
NSAIDs, and glucocorticoids are the last resort. The initiation of empirical therapy
does not mark the end of the diagnostic workup; rather, it commits the physician
to continued thoughtful reexamination and evaluation. Patience, compassion,
equanimity, and intellectual flexibility are indispensable attributes for the
clinician in dealing successfully with FUO.
40. Hypothermia
• Accidental hypothermia occurs when there is an unintentional drop in
the body's core temperature below 35°C (95°F). At this temperature,
many of the compensatory physiologic mechanisms to conserve heat
begin to fail. Primary accidental hypothermia is a result of the direct
exposure of a previously healthy individual to the cold. The mortality
rate is much higher for those patients who develop secondary
hypothermia as a complication of a serious systemic disorder.
41.
42. • Primary accidental hypothermia is geographically and seasonally pervasive.
Although most cases occur in the winter months and in colder climates, it is
surprisingly common in warmer regions as well. Multiple variables make
individuals at the extremes of age, the elderly and neonates, particularly
vulnerable to hypothermia. The elderly have diminished thermal
perception and are more susceptible to immobility, malnutrition, and
systemic illnesses that interfere with heat generation or conservation.
Dementia, psychiatric illness, and socioeconomic factors often compound
these problems by impeding adequate measures to prevent hypothermia.
Neonates have high rates of heat loss because of their increased surface-
to-mass ratio and their lack of effective shivering and adaptive behavioral
responses. In addition, malnutrition can contribute to heat loss because of
diminished subcutaneous fat and because of depleted energy stores used
for thermogenesis.
43. • Individuals whose occupations or hobbies entail extensive exposure
to cold weather are at increased risk for hypothermia. Military history
is replete with hypothermic tragedies. Hunters, sailors, skiers, and
climbers also are at great risk of exposure, whether it involves injury,
changes in weather, or lack of preparedness.
• Ethanol causes vasodilatation (which increases heat loss), reduces
thermogenesis and gluconeogenesis, and may impair judgment or
lead to obtundation. Phenothiazines, barbiturates, benzodiazepines,
cyclic antidepressants, and many other medications reduce centrally
mediated vasoconstriction. Up to 25% of patients admitted to an
intensive care unit because of drug overdose are hypothermic.
Anesthetics can block the shivering responses; their effects are
compounded when patients are not covered adequately in the
operating or recovery rooms.
44. • Several types of endocrine dysfunction can lead to hypothermia.
Hypothyroidism—particularly when extreme, as in myxedema coma—
reduces the metabolic rate and impairs thermogenesis and behavioral
responses. Adrenal insufficiency and hypopituitarism also increase
susceptibility to hypothermia. Hypoglycemia, most commonly caused by
insulin or oral hypoglycemic drugs, is associated with hypothermia, in part
the result of neuroglycopenic effects on hypothalamic function. Increased
osmolality and metabolic derangements associated with uremia, diabetic
ketoacidosis, and lactic acidosis can lead to altered hypothalamic
thermoregulation.
• Neurologic injury from trauma, cerebrovascular accident, subarachnoid
hemorrhage, or hypothalamic lesions increases susceptibility to
hypothermia. Agenesis of the corpus callosum, or Shapiro syndrome, is one
cause of episodic hypothermia, characterized by profuse perspiration
followed by a rapid fall in temperature. Acute spinal cord injury disrupts
the autonomic pathways that lead to shivering and prevents cold-induced
reflex vasoconstrictive responses.
45. • Hypothermia associated with sepsis is a poor prognostic sign. Hepatic
failure causes decreased glycogen stores and gluconeogenesis, as well
as a diminished shivering response. In acute myocardial infarction
associated with low cardiac output, hypothermia may be reversed
after adequate resuscitation. With extensive burns, psoriasis,
erythrodermas, and other skin diseases, increased peripheral blood
flow leads to excessive heat loss
47. Diagnosis and Stabilization
• Hypothermia is confirmed by measuring the core temperature, preferably
at two sites. Rectal probes should be placed to a depth of 15 cm and not
adjacent to cold feces. A simultaneous esophageal probe should be placed
24 cm below the larynx; it may read falsely high during heated inhalation
therapy. Relying solely on infrared tympanic thermography is not advisable.
• After a diagnosis of hypothermia is established, cardiac monitoring should
be instituted, along with attempts to limit further heat loss. If the patient is
in ventricular fibrillation, one defibrillation attempt (2 J/kg) should be
administered. If the rhythm does not convert, rewarm the patient to 30–
32°C before repeating defibrillation attempts. Supplemental oxygenation is
always warranted, since tissue oxygenation is adversely affected by the
leftward shift of the oxyhemoglobin dissociation curve. Pulse oximetry may
be unreliable in patients with vasoconstriction. If protective airway reflexes
are absent, gentle endotracheal intubation should be performed. Adequate
pre-oxygenation will prevent ventricular arrhythmias. Although cardiac
pacing for hypothermic bradydysrhythmias is rarely indicated, the
transthoracic technique is preferable.
48. • Insertion of a gastric tube prevents dilatation secondary to decreased
bowel motility. Indwelling bladder catheters facilitate monitoring of cold-
induced diuresis. Dehydration is commonly encountered with chronic
hypothermia, and most patients benefit from a bolus of crystalloid. Normal
saline is preferable to lactated Ringer's solution, as the liver in hypothermic
patients inefficiently metabolizes lactate. The placement of a pulmonary
artery catheter risks perforation of the less compliant pulmonary artery.
Insertion of a central venous catheter into the cold right atrium should be
avoided, since this can precipitate arrhythmias.
• Arterial blood gases should not be corrected for temperature (Chap. 48).
An uncorrected pH of 7.42 and a PCO2 of 40 mmHg reflects appropriate
alveolar ventilation and acid-base balance at any core temperature. Acid-
base imbalances should be corrected gradually, since the bicarbonate
buffering system is inefficient. A common error is overzealous
hyperventilation in the setting of depressed CO2 production. When the PCO2
decreases 10 mmHg at 28°C, it doubles the pH increase of 0.08 that occurs
at 37°C.
49. • The severity of anemia may be underestimated because the hematocrit
increases 2% for each 1°C drop in temperature. White blood cell
sequestration and bone marrow suppression are common, potentially
masking an infection. Although hypokalemia is more common in chronic
hypothermia, hyperkalemia also occurs; the expected electrocardiographic
changes can be obscured by hypothermia. Patients with renal insufficiency,
metabolic acidoses, or rhabdomyolysis are at greatest risk for electrolyte
disturbances.
• Coagulopathies are common because cold inhibits the enzymatic reactions
required for activation of the intrinsic cascade. In addition, thromboxane B2
production by platelets is temperature-dependent, and platelet function is
impaired. The administration of platelets and fresh frozen plasma is,
therefore, not effective. The prothrombin or partial thromboplastin times
or INR (international normalized ratio) reported by the laboratory appear
deceptively normal and contrast with the observed in vivo coagulopathy.
This contradiction occurs because all coagulation tests are routinely
performed at 37°C, and the enzymes are thus rewarmed.
50. Rewarming Strategies
• The key initial decision is whether to rewarm the patient passively or actively.
Passive external rewarming simply involves covering and insulating the patient in
a warm environment. With the head also covered, the rate of rewarming is
usually 0.5° to 2.0°C per hour. This technique is ideal for previously healthy
patients who develop acute, mild primary accidental hypothermia. The patient
must have sufficient glycogen to support endogenous thermogenesis.
• The application of heat directly to the extremities of patients with chronic severe
hypothermia should be avoided because it can induce peripheral vasodilatation
and precipitate core temperature "afterdrop"—a response characterized by a
continual decline in the core temperature after removal of the patient from the
cold. Truncal heat application reduces the risk of afterdrop.
• Active rewarming is necessary under the following circumstances: core
temperature < 32°C (poikilothermia), cardiovascular instability, age extremes, CNS
dysfunction, hormone insufficiency, or suspicion of secondary hypothermia.
Active external rewarming is best accomplished with forced-air heating blankets.
Other options include radiant heat sources and hot packs. Monitoring a patient
with hypothermia in a heated tub is extremely difficult. Electric blankets should
be avoided because vasoconstricted skin is easily burned.
51. • There are numerous widely available active core rewarming options.
Airway rewarming with heated humidified oxygen (40°–45°C) is a
convenient option via mask or endotracheal tube. Although airway
rewarming provides less heat than some other forms of active core
rewarming, it eliminates respiratory heat loss and adds 1°–2°C to the
overall rewarming rate. Crystalloids should be heated to 40°–42°C, but the
quantity of heat provided is significant only during massive volume
resuscitation. The most efficient method for heating and delivering fluid or
blood is with a countercurrent in-line heat exchanger. Heated irrigation of
the gastrointestinal tract or bladder transfers minimal heat because of the
limited available surface area. These methods should be reserved for
patients in cardiac arrest and then used in combination with all available
active rewarming techniques.
52. • Closed thoracic lavage is far more efficient in severely hypothermic patients
with cardiac arrest. The hemithoraces are irrigated through two large-bore
thoracostomy tubes that are inserted into the hemithoraces. Thoracostomy
tubes should not be placed in the left chest of a spontaneously perfusing
patient for purposes of rewarming. Peritoneal lavage with the dialysate at
40°–45°C efficiently transfers heat when delivered through two catheters
with outflow suction. Like peritoneal dialysis, standard hemodialysis is
especially useful for patients with electrolyte abnormalities,
rhabdomyolysis, or toxin ingestions.
53. • Extracorporeal blood rewarming options should be considered in
severely hypothermic patients, especially those with primary
accidental hypothermia. Cardiopulmonary bypass should be
considered in nonperfusing patients without documented
contraindications to resuscitation. Circulatory support may be the
only effective option in patients with completely frozen extremities,
or those with significant tissue destruction coupled with
rhabdomyolysis. There is no evidence that extremely rapid rewarming
improves survival in perfusing patients. The best strategy is usually a
combination of passive, truncal active, and active core rewarming
techniques.
54.
55. Hypothermia: Treatment
• When a patient is hypothermic, target organs and the cardiovascular system
respond minimally to most medications. Moreover, cumulative doses can cause
toxicity during rewarming because of increased binding of drugs to proteins, and
impaired metabolism and excretion. As an example, the administration of
repeated doses of digoxin or insulin would be ineffective while the patient is
hypothermic, and the residual drugs are potentially toxic during rewarming.
• Achieving a mean arterial pressure of at least 60 mmHg should be an early
objective. If the hypotension does not respond to crystalloid/colloid infusion and
rewarming, low-dose dopamine (2–5 g/kg per min) support should be
considered. Perfusion of the vasoconstricted cardiovascular system may also be
improved with low-dose IV nitroglycerin.
56. • Atrial arrhythmias should initially be monitored without intervention, as
the ventricular response will be slow, and unless preexistent, most will
convert spontaneously during rewarming. The role of prophylaxis and
treatment of ventricular arrhythmias is problematic. Preexisting ventricular
ectopy may be suppressed by hypothermia and reappear during
rewarming. None of the class I agents has proved to be safe and
efficacious. When available, bretylium tosylate was the class III ventricular
antiarrhythmic of choice. There is no evidence that amiodarone is safe.
• Initiating empirical therapy for adrenal insufficiency is usually not
warranted unless there is a history suggesting steroid dependence,
hypoadrenalism, or a failure to rewarm with standard therapy. The
administration of parenteral levothyroxine to euthyroid patients with
hypothermia, however, is potentially hazardous. Because laboratory results
can be delayed and confounded by the presence of the sick euthyroid
syndrome (Chap. 335), historic clues or physical findings suggestive of
hypothyroidism should be sought. When myxedema is the cause of
hypothermia, the relaxation phase of the Achilles reflex is prolonged more
than the contraction phase.
57. • Hypothermia obscures most of the symptoms and signs of infection,
notably fever and leukocytosis. Shaking rigors from infection may be
mistaken for shivering. Except in mild cases, extensive cultures and
repeated physical examinations are essential. Unless an infectious
source is identified, empirical antibiotic prophylaxis is most warranted
in the elderly, neonates, and immunocompromised patients.
• Preventive measures should be discussed with high-risk individuals,
such as the elderly or people whose work frequently exposes them to
extreme cold. The importance of layered clothing and headgear,
adequate shelter, increased caloric intake, and the avoidance of
ethanol should be emphasized, along with access to rescue services.
