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Yellow Fever: Treatment & Medication
Updated: Oct 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Prehospital Care
Patients with yellow fever with hemodynamic instability should undergo prehospital fluid resuscitation. Adherence to universal precautions is mandatory to prevent transmission to health care workers.
Emergency Department Care
Treatment of yellow fever is principally symptomatic and preventative.
- Closely monitor patients for hypovolemia, oliguria, hypoxia, acidosis, and electrolyte imbalance. Hypotension and hypoxia may aggravate hepatic and renal injury.
- Invasive arterial blood pressure monitoring may be warranted.
- Intravascular volume may decrease secondary to sequestration in the extravascular space or to fluid loss through insensible losses, vomiting, and capillary leak.
- If oxygenation and hydration do not improve hemodynamic parameters, or if myocardial dysfunction is present, monitor pulmonary artery pressures.
- Monitor central venous pressure, peripheral blood pressure, as well as surrogates for organ perfusion and regional blood flow (eg, capillary refill, urinary output, ScvO2). Swan-Ganz catheter monitoring of hemodynamic parameters may be helpful in some situations.
- Monitor acid-base disturbances and metabolic acidosis via arterial blood gas sampling
- Use of cooling blankets and tepid sponging can reduce fever and, thus, oxygen consumption.
- Hypothermia frequently occurs late in the disease course and is corrected with gradual rewarming.
- Nasogastric suction is essential to prevent gastric distention and aspiration of gastric contents. H2-receptor antagonists and sucralfate may also be valuable in preventing gastric bleeding.
- Consider parenteral alimentation. Hypoglycemia can be prevented by infusion of 10-20% glucose solution.
- Replacement of red blood cells, clotting components, and other volume expanders are used to treat hemorrhage and shock.
- Renal failure may necessitate dialysis. Consider dopamine for patients not responding to hydration, but dobutamine may offer the advantage of its positive chronotropic effect. Avoid drugs that are dependent on hepatic metabolism while medication doses should be adjusted for reduced renal function.
Consultations
- Intensivist consultation for severe disease or hemorrhagic fever
- Infectious disease consultation
- Centers for Disease Control and Prevention/reportable disease
Medication
Currently, no antiviral drug against yellow fever is approved. To date, nonclinical testing of antiviral agents has yielded modest results. Ribavirin, given at high doses to hamsters challenged with yellow fever, has been shown to reduce mortality when administered as late as 120 hours after infection. Interferon-α has also been found to reduce mortality when administered to monkeys with yellow fever; however, it was only effective when given within 24 hours of infection. These findings suggest that antiviral therapies may only be effective early in the course of disease when clinical symptoms are nonspecific and indistinguishable from other viral infections. Recent trials by Julander et al involving an active carboxamide drug [AT-1106 (2,4-dihydro-3-oxo-4-β-D-ribofuranosyl-2-pyrazinecarboxamide)] have been effective in hamsters when treatment was started on day 4, after the development of liver infection.5 Ongoing research and advances show promise for the future.Adjunctive measures include nonhepatotoxic antipyretics to reduce fever and pain and an H2-receptor antagonist to prevent gastric bleeding. Use of heparin for documented cases of DIC is controversial. Additionally, the use of stress-dose corticosteroids is currently under investigation.5 Avoid drugs that act centrally, including phenothiazines, barbiturates, and benzodiazepines, because they may precipitate or aggravate encephalopathy. Avoid drugs dependent on hepatic metabolism, and, in cases of reduced renal function, medications should be renally dosed.
Histamine H2 antagonists
These agents are useful as an adjunctive therapy to prevent gastric bleeding. H2-receptor antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents. These are potent inhibitors of all phases of gastric acid secretion. They inhibit secretions caused by histamine, muscarinic agonists, and gastrin.
Famotidine (Pepcid)
Competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.
Adult
20-40 mg PO qhs or 20 mg IV q12h
Pediatric
0.5 mg/kg PO/IV qh; not to exceed 40 mg/d
May decrease efficacy of ketoconazole, itraconazole, cefpodoxime, delavirdine, digestive enzymes, and iron salts
Documented hypersensitivity; phenylketonuria; impaired renal function
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
If changes in renal function occur during therapy, adjust dose or discontinue treatment; serious reactions include thrombocytopenia, leukopenia, pancytopenia, and cholestatic jaundice
Nizatidine (Axid)
Competitively inhibits histamine at the H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.
Adult
300 mg PO hs or 150 mg bid
Pediatric
<6 months: Not established
6-10 mg/kg PO qd (for 6 months to 12 years, divide dose bid)
>12 years: Administer as in adults
May reduce efficacy of cefpodoxime, delavirdine, digestive enzymes, iron salts, and ketoconazole
Documented hypersensitivity; impaired renal function
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
If changes in renal function occur during therapy, adjust dose or discontinue treatment; serious reactions include thrombocytopenia, leukopenia, pancytopenia, and cholestatic jaundice
Ranitidine (Zantac)
Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.
Adult
150 mg PO bid or 300 mg PO qhs; alternately, 50 mg/dose IV/IM q6-8h
Pediatric
<2 weeks: 2 mg/kg PO divided bid ; alternately, 1.5 mg/kg IV initial, then 1.5 mg/kg IV divided bid
Infusion: 0.04 mg/kg/h IV
Children: 4-5 mg/kg PO IV/IM divided bid/tid; alternately, 2-4 mg/kg IV/IM divided tid/qid; infusion 0.1-0.125 mg/kg/h
May decrease effects of ketoconazole, itraconazole, cefpodoxime, delavirdine, and digestive enzymes; may alter serum levels of ferrous sulfate, nondepolarizing muscle relaxants, diazepam, and oxaprozin
Documented hypersensitivity; porphyria; impaired liver and renal function
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dosage or discontinuing treatment; may cause thrombocytopenia and hepatotoxicity
Antipyretics
Treatment of yellow fever is symptomatic and supportive. Bed rest and mild analgesic-antipyretic therapy often help relieve associated lethargy, malaise, and fever.
Acetaminophen (Tylenol, Aspirin-Free Anacin, Feverall)
Inhibits action of endogenous pyrogens on heat-regulating centers; reduces fever by direct action on the hypothalamic heat-regulating centers, which, in turn, increase dissipation of body heat via sweating and vasodilation.
Adult
325-1000 mg PO/PR q4-6h; not to exceed 4 g/d
Alternatively, administer 1000 mg tid/qid; not to exceed 4 g/d
Pediatric
<12 years: 10-15 mg/kg/dose PO/PR q4-6h prn; not to exceed 2.6 g/d
>12 years: 325-650 mg PO/PR q4h; not to exceed 4 g/d
Because of induction of microsomal enzymes by barbiturates, carbamazepine, hydantoins, isoniazid, rifampin, and sulfinpyrazone, long-term administration of these agents or large doses of acetaminophen may increase acetaminophen hepatotoxicity (therapeutic effects of acetaminophen also may decrease)
Documented hypersensitivity; G-6-PD deficiency, phenylketonuria, impaired liver and renal function, and long-term alcohol use
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hepatotoxicity possible in patients with chronic alcoholism following various dose levels; severe or recurrent pain or high or continued fever may indicate serious illness; acetaminophen is contained in many OTC products and combined use with these products may result in cumulative acetaminophen doses exceeding recommended maximum dose
Aspirin (Anacin, Bufferin, Ecotrin)
Lowers elevated body temperature by vasodilating peripheral vessels, thereby enhancing dissipation of excess heat. Also acts on the heat-regulating center of hypothalamus to reduce fever.
Adult
325-650 mg PO/PR q4h
Pediatric
10-15 mg/kg PO/PR q4-6h; not to exceed 60-80 mg/kg/d
Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants, antiplatelets, COX-2 inhibitors, sulfinpyrazone, thrombolytics, and valproic acid derivatives; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs and insulin; mesalamine may increase aspirin toxicity; combo therapy may increase methotrexate toxicity
Documented hypersensitivity; liver damage, GERD, G-6-PD deficiency, hypoprothrombinemia, TTP, vitamin K deficiency, bleeding disorders, asthma; because of association of aspirin with Reye syndrome, do not use in children (<16 y) with flu
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants
Ibuprofen (Motrin, Advil, Nuprin)
NSAID with analgesic and antipyretic activities. Although exact mode of action not known, appears to inhibit cyclooxygenase activity and prostaglandin synthesis. May inhibit lipoxygenase, leukotriene synthesis, lysosomal enzyme release, neutrophil aggregation, and various cell-membrane functions.
Adult
200-400 mg PO q4-6h prn; not to exceed 3.2 g/d; take with food
Pediatric
4-10 mg/kg PO q6-8h, not to exceed 50 mg/kg/d; take with food
Coadministration with aspirin, probenecid, and leflunomide increases risk of inducing serious NSAID-related adverse effects; anticoagulants, antiplatelets, corticosteroids, COX-2 inhibitors, thrombolytics, valproic acid derivatives, and aspirins may increase risk of bleeding; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, ACE inhibitors, angiotensin II receptor blockers, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase lithium toxicity, phenytoin levels may be increased when administered concurrently, acetaminophen, cyclosporin, may increase risk of nephrotoxicity, all quinolones may increase risk of CNS stimulation
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding; CHF
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy
More on Yellow Fever |
| Overview: Yellow Fever |
| Differential Diagnoses & Workup: Yellow Fever |
 Treatment & Medication: Yellow Fever |
| Follow-up: Yellow Fever |
| Multimedia: Yellow Fever |
| References |
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References
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Further Reading
Keywords
yellow fever symptoms, yellow fever vaccine, flavivirus, , group B arbovirus, attenuated 17D vaccine, flaviviral infections, dengue, Japanese encephalitis, tick-borne encephalitis, hemorrhagic fever, acute febrile illnesses with arthropathy
