Page 830 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 63: Persistent Fever 561

vasoconstriction. Antipyretics, such as ibuprofen and other nonsteroi-
6
TABLE 63-2 Drugs That May Precipitate Serotonin Syndrome
dal anti-inflammatory drugs (NSAIDS), work by blocking PGE produc-
2
Antidepressants/antipsychotics Headache, nausea, antiepileptics tion via cyclooxygenase inhibition. The physiological effects of this
74
Monoamine oxidase inhibitors Triptans blockade result in vasodilation and sweating, leading to heat dissipation.
Selective serotonin reuptake inhibitor Valproate Ibuprofen is available in oral and intravenous formulations and has the
Serotonin-norepinephrine reuptake inhibitors Carbamazepine added benefit of improving patient comfort by its analgesic and anti-
Tricyclic antidepressants Ergot alkaloids inflammatory effects.
Tetracyclic antidepressants Ondansetron Acetaminophen is a para-aminophenol derivative that is avail-
Trazodone Metoclopramide able in oral, rectal, and intravenous formulations. It appears to have
Tranylcypromine Anti-infectives a direct action on thermogenesis at the level of the hypothalamus.
5-Hydroxytryptophan Linezolid Acetaminophen has less anti-inflammatory effect than ibuprofen but it
Buspirone Ritonavir has similar analgesic and antipyretic properties. It may be favored over
Olanzapine Stimulants/psychedelics ibuprofen in patients with gastrointestinal bleeding, coagulopathy, or
Lithium Cocaine kidney disease.
Opiates Methamphetamines
Fentanyl Dextromethorphan ■ COOLING
Methadone Miscellaneous Attempts to lower body temperature by external cooling utilizing con-
Meperidine Cyclobenzaprine
Tramadol Methylene blue vection, conduction, and evaporation are as old as mankind. Removal
of blankets and clothing and the use of air convection with tepid water
St John wort
sponging are time-honored interventions. More aggressive measures,
such as use of ice packs and cool saline infusions, are usually used in
cases of severe hyperthermia with core body temperature above 40°C
(see above). Modern intensive care units often have more sophisticated
commonly implicated. The syndrome has also been associated approaches, such as water-circulating blankets and intravascular heat
70
with abrupt withdrawal of dopamine agonists, such as L-dopa or exchangers. In a study of 50 intensive care patients, temperature decline
baclofen. Treatment of NMS is centered on supportive care, cooling, was significantly faster with water-circulating blankets and intravas-
75
and administration of the central nervous system dopaminergic drug, cular heat exchanging devices than with conventional treatment.
bromocriptine. Dantrolene sodium may be administered to abolish The intravascular cooling devices were found to be the most efficient
71
excitation-contraction coupling in skeletal muscles and benzodiaz- for reaching the target temperature with the least temperature vari-
75
epines can be useful to control agitation. ability. In a separate study, water-circulating blankets were found to
be effective even in patients refractory to pharmacologic methods of
■ MALIGNANT HYPERTHERMIA antipyresis. When core body temperature must be rapidly reduced,
65
such as in heat stroke, it is advised to place a water-circulating blanket
Malignant hyperthermia is a genetic muscle membrane disorder that both under and on top of the patient. Placing a wet sheet between each
causes the excess propagation of calcium ions within skeletal muscle water-circulating blanket and the patient will further increase conduc-
myocytes following challenge with volatile halogenated anesthetics tive heat transfer.
72
or succinylcholine. The exaggerated calcium flux then leads to excess Data remain inconclusive on the impact of temperature reduction on
thermogenesis. Hyperthermia and hypercarbia usually develop within clinically important outcomes among febrile critically ill patients. In a
30 minutes of exposure to the offending agent. The dominant inheri- randomized, double-blind, controlled trial of 455 patients with sepsis,
tance of a single mutation in ryanodine receptors integral to excitation- treatment with ibuprofen, as compared to placebo, lowered temperature,
contraction coupling in myocytes accounts for approximately 20% of all heart rate, oxygen consumption, and lactic acid levels but did not reduce
genetically transmitted malignant hyperthermia. Prompt withdrawal of the incidence or duration of shock, the incidence of ARDS, or mortality
the offending drug, cooling, and treatment with dantrolene sodium can at 30 days. 76
be lifesaving. In a separate trial of 38 intensive care patients with a rectal tempera-
ture of >38.5°C, subjects were randomized to treatment with a cooling
blanket or to no antipyretic treatment. Both groups had similar rates of
77
TREATMENT OF FEVER death, infection, length of ICU stay, and recurrence of fever.
The most important question to be answered is: “When should fever be In a third trial, investigators randomized non-head-injured patients
78
treated?” Outside of the realm of neurocritical care, there is no consen- to either an aggressive or permissive temperature treatment regimen.
sus about the answer to this question. On the one hand, fever is a natural The aggressive treatment group received scheduled acetaminophen
occurrence during infection and trauma that may provide benefits to for temperature of >38.5°C and an additional cooling blanket if tem-
the host as discussed above. On the other hand, the hypermetabolism perature exceeded 39.5°C. The permissive group had no intervention
associated with fever can add metabolic stress to a patient with already unless temperature reached >40°C at which point acetaminophen and
limited reserve. Finally, before making a decision to treat a fever, it cooling blankets were initiated but these interventions were withdrawn
is important to first consider the potential deleterious effects of the as soon as temperature was below 40°C. This study was halted prema-
planned therapy on organ function, for example, NSAIDS can aggravate turely because the aggressively treated group developed more infec-
acute kidney injury. tions compared to the permissive group (131 vs 85, respectively) and
the aggressive treatment group had a significantly higher rate of death
■ ANTIPYRETIC DRUGS (7 vs 1 patients, respectively).
Finally, in a recent multicenter trial, 200 febrile patients with
The most commonly used antipyretics in the ICU are acetaminophen vasopressor-dependent septic shock were randomized to external cool-
and ibuprofen. The choice between these two drugs should include ing to achieve normothermia for 48 hours or to no external cooling.
careful consideration of underlying hepatic, renal, and gastrointestinal The external cooling group was significantly more likely to have shock
disease. 73 reversal during the intensive care unit stay (86% vs 73%, respectively).
Release of PGE within the preoptic nucleus of the anterior hypo- The external cooling group also had lower early mortality than the
2
thalamus increases sympathetic activity, induces shivering, and causes control group (day 14 mortality 19% vs 34%, respectively). 79

section05_c61-73.indd 561 1/23/2015 12:47:20 PM