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Critical Care Viral Infections
Objectives
This chapter will:
- 1.
Describe the diagnosis and treatment of viral influenza.
- 2.
Explain the evaluation and management of viral meningoencephalitis.
- 3.
Describe the initial approach to viral hepatitis.
Viral infections in the intensive care unit (ICU) have gained a higher profile recently. This is due, in part, to novel and emerging pathogens, an aging population, and increased numbers of immunocompromised hosts, but most of the apparent increase is due to ready availability of molecular testing. Many cases of sepsis that would have been unidentified previously are now known to be viruses. Intensivists thus must have a thorough understanding of viral syndromes.
Although viruses can infect every organ system ( Table 96.1 ), three syndromes predominate in immunocompetent adults. These are respiratory, central nervous system (CNS), and gastrointestinal infection. Other populations, such as transplant and human immunodeficiency virus (HIV) patients, are discussed in Chapter 46 .
TABLE 96.1
Etiology and Treatment of Viral Infections in the ICU
| SYNDROME/PRESENTATION | COMMON VIRUSES | TREATMENT |
|---|---|---|
| Respiratory Failure | ||
| Hypoxic respiratory failure-pneumonia | Hypoxic respiratory failure: Influenza A and B, RSV A and B, coronavirus, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome coronavirus, Adenovirus, cytomegalovirus, Varicella, HSV, Parainfluenza 1-4, Metapneumovirus, measles especially in immunocompromised patients | Supportive: adequate oxygen delivery |
| VAP: HSV, CMV, Mimivirus | ||
| Hypercapnic-hypoxic respiratory failure | Hypercapnic-hypoxic respiratory failure: Influenza A and B, coronavirus, rhinovirus, Parainfluenza 1-4, RSV A and B | Antivirals: Neuraminidase inhibitors (NAIs) (Oseltamivir, Zanamivir, peramivir, Laninamivir). For resistant influenza viruses may consider combination therapy of NAI with ribavirin and/or novel antivirals such as Favipiravir |
| Asthma/COPD exacerbation | ||
| Adult Respiratory Distress Syndrome (ARDS) | ARDS: Influenza virus, Hantavirus [Hantavirus pulmonary syndrome (HPS)], varicella, herpes simplex virus, SARS, MERS-CoV | Ribavirin for RSV in immunocompromised patients and children and may also be considered for other viruses such as in SARS or MERS-CoV - lopinavir in combination regimens has also been used |
| Without lung disease (restrictive disease): Guillain-Barré syndrome (GBS) | GBS: HSV, VZV, CMV, EBV, Influenza, Hantavirus acute and chronic hepatitis B, Rare causes: West Nile virus, Parvovirus B19, Hantavirus, rubella, dengue | Acyclovir for VZV pneumonitis (limited efficacy it is still widely recommended as early primary therapy) |
| Ganciclovir for CMV pneumonitis in solid organ transplant patients appears to reduce morbidity | ||
| Corticosteroids: For influenza, SARS and VZV pneumonitis to reduce inflammatory tissue injury in severe pneumonia | ||
| Immunotherapies: Palivizumab is approved for high-risk pediatric patients with RSV infection; IVIG for certain respiratory viruses including influenza and GBS, plasma exchange for GBS. Combinations of ganciclovir with immunoglobulin or cytomegalovirus immunoglobulin may be of value in patients with bone marrow transplants and CMV pneumonitis. | ||
| Others: Vitamin A for severe measles | ||
| Neurological syndromes | ||
| Encephalitis, meningitis, meningoencephalitis, myelitis, polyradiculo-neuropathy, Guillain-Barré syndrome (GBS) Reyes syndrome, subacute sclerosing panencephalitis, postinfectious acute disseminated encephalomyelitis (ADEM) | HSV: 40% to 50% of encephalitis cases where a cause is determined, and 10% to 20% overall VZV (the most common cause of encephalitis among immunocompromised patients and the second most common viral cause of sporadic encephalitis not occurring during an outbreak) | Supportive: Treatment of neurologic (eg, cerebral edema, high intracranial pressure, and seizures) and systemic (eg, hypoxemia, low cerebral perfusion pressure, and fever) complications |
| Clinical presentation: usually as altered mental status, seizures, coma, neuropathies | Enteroviruses (Enterovirus 71, Coxsackie, Echovirus, poliovirus: as a group, enteroviruses) are collectively the third most common cause of sporadic viral encephalitis and the most common cause of aseptic meningitis. | Antivirals: Acyclovir: early aggressive antiviral therapy with acyclovir for HSV, VZV improves mortality and reduces subsequent cognitive impairment |
| Arboviruses (JEV, WNV, TBEV, MVEV, LCEV, SLEV, EEEV: the most common pathogens to cause encephalitis that is restricted to certain geographic regions) | ||
| Influenza (encephalitis is very uncommon complication of seasonal influenza infections but because influenza itself is common 4-19% of patients with severe or fatal H1N1 reported neurologic complications) | Ganciclovir: CMV encephalitis | |
| Other viruses: West Nile virus, CMV, mumps, measles, rubella, rabies, JC virus (PML), acute HIV infection | Foscarnet: HHV-6, combination therapy with foscarnet and ganciclovir is recommended for CMV encephalitis | |
| Oseltamivir: severe influenza | ||
| Pleconaril: severe Enterovirus infections | ||
| Corticosteroids: complicated HSV encephalitis (data based on retrospective studies), VZV encephalitis (for inflammatory vasculopathy), uncomplicated zoster (variable results), severe influenza, WNV (case report), postinfectious encephalitis | ||
| Immunotherapies: immunomodulatory therapy with either intravenous immune globulin or plasma exchange for patients with postinfectious encephalitis who fail corticosteroid treatment (data based on case series) or for WNV encephalitis (Case reports) | ||
| Others: Vitamin A for severe measles | ||
| Virus related shock | ||
| Cardiogenic shock | Enteroviruses (Enterovirus 71, Coxsackie viruses group A and B, Echovirus), Influenza, Adenovirus, Parvovirus, RSV, CMV, HIV-1, hepatitis A and C viruses, vaccinia virus (after smallpox vaccine) | Supportive |
| Myocarditis | Antivirals: | |
| Rifampin: for RSV myocarditis | ||
| Pleconaril: severe Enterovirus infections | ||
| Oseltamivir: severe influenza | ||
| ART: HIV-1 | ||
| Corticosteroids: do not reduce mortality (data based on small RCT of poor quality) | ||
| Immunotherapies: IVIG (data based on in vitro data, case series, limited RCT.) Combination therapy of IVIG with rifampin has been described in case series. | ||
| Others: herbal medicines, mechanical ventricular assist devices until resolution or cardiac transplantation is available, novel therapies e.g pleconaril | ||
| Distributive shock-Hemorrhagic fever | Arenaviruses (South American HF-Junin; Lassa Fever), Bunyaviruses (Rift valley fever, Crimean Congo HF-CCHF), HF with renal syndrome, Hantavirus, Filoviruses (Ebola, Marburg), Flaviviruses (Yellow fever, Dengue HF) | Supportive: adequate oxygen delivery, blood products. |
| Clinical presentation: febrile illnesses, headache, myalgia, nausea, vomiting and diarrhea are frequent. Hemorrhagic features, disseminated intravascular coagulopathy (DIC), multiple organ system failure and death ensue. | Passive transfer of antibodies (plasma, IVIG) may be of value in Bunyaviruses, Junin virus, Lassa virus, Hantavirus HF, Flaviviruses (Yellow fever, Dengue HF) | |
| Antivirals: ribavirin for CCHF , Lassa virus, Hantavirus HF | ||
| Ribavirin plus interferon may be considered for Lassa virus | ||
| Hypovolemic/distributive shock in the setting of acute liver failure secondary to viral hepatitis | Hepatitis A, B, C, D, E, G, herpes group (CMV, HSV and Epstein Barr virus), adenovirus and influenza virus | Supportive: hemodynamic management, ventilation, prevention and treatment of hemorrhage, dialysis, therapy of co-existent sepsis and electrolyte disturbance, and management of intracranial pressure |
| Clinical presentation: nausea and vomiting with progression to encephalopathy and coma; may be new onset or acute decompensation of chronic liver failure due to viral hepatitis/cirrhosis | Orthotopic liver transplantation | |
| Antivirals (may be used for acute flare up of chronic viral hepatitis e.g. in immunocompromised patients) | ||
| Hypovolemic/distributive shock in the setting of acute pancreatitis | Mumps (the most common virus associated with pancreatitis, occurring even in the absence of parotitis), Enteroviruses (Coxsackie B), cytomegalovirus, varicella zoster, HSV-1, Epstein-Barr virus, influenza A, Parainfluenza, adenovirus, measles. In fulminant hepatic failure due to hepatitis A (HAV) or hepatitis E (HEV) pancreatitis occurs in up to 34% of the cases | Supportive |
| Antivirals | ||
| Oseltamivir: severe influenza | ||
| Pleconaril: severe Enterovirus infections | ||
| Acyclovir: VZV | ||
| Shock in the setting of adrenal insufficiency caused by viral infection (rare) | CMV in HIV-1 infection | Treatment of CMV itself is generally not warranted, unless there is evidence of CMV disease elsewhere. However, it is critical to treat the underlying human immunodeficiency virus infection with antiretroviral agents to attempt immune restitution. |
| Rhabdomyolysis | Influenza A and B, Parainfluenza virus, CMV, EBV, VZV, measles, adenovirus, enteroviruses | Supportive |
| Antivirals | ||
| Oseltamivir: severe influenza | ||
| Pleconaril: severe Enterovirus infections | ||
| Acyclovir: VZV | ||
| Ganciclovir: CMV | ||
| Special Immunocompromised host | ||
| Trauma/Burn | HSV, CMV | Supportive, antivirals, corticosteroids |
| Pregnancy | HSV, VZV, CMV, Influenza virus | Supportive, antivirals |
| Transplantation | CMV, EBV (post-transplant lymphoproliferative disorder [PTLD]), VZV, HSV, HHV-6 and HHV-8, RSV, Influenza A and B, BK virus, Adenovirus | Supportive, antivirals, immunotherapies (for example donor lymphocyte infusions and anti-CD20 antibody for PTLD), experimental therapies |
Abbreviations: ADEM, acute disseminated encophalomyelitis; ARDS, Adult Respiratory Distress Syndrome; CMV, Cytomegalovirus; CCHF, Crimean Congo Hemorrhagic Fever; COPD, Chronic Obstructive Pulmonary Disease; DIC, disseminated intravascular coagulopathy; EBV, Epstein Barr virus; GBS, Guillain-Barré syndrome; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HEV, hepatitis E virus; HIV, human immunodeficiency virus; HHV-6, Herpes Virus 6; HHV-8, Herpes Virus 8; HF, Hemorrhagic Fever; HSV, Herpes Simplex Virus; NAIs, Neuraminidase inhibitors; ICU, Intensive Care Unit; JEV, Japanese Encephalitis Virus; MVEV, Murray Valley encephalitis virus; PTLD, post-transplant lymphoproliferative disorder; RCT, Randomized Controlled trials; RSV, Respiratory Syncytial Virus; SARS, Severe Acute Respiratory Syndrome; TBEV, tick-borne encephalitis virus; SLEV, St. Louis Encephalitis Virus; VZV, Varicella-Zoster Virus; WNV, West Nile virus.
Reprinted under a Creative Commons Attribution License from Kelesendis T, Mastoris I, Metsini A and Tsiodras S. How to Approach and Treat Viral Infections in ICU patients. BMC Infectious Diseases. 2014; 14:321 DOI: 10.1186/1471-2334-14-321.
Central Nervous System Infections
The most common acute viral infections of the CNS are aseptic meningitis and encephalitis. Meningitis is inflammation of the meningeal layers surrounding the brain, involving headache, fevers, and meningismus. Encephalitis involves the brain parenchyma and alterations of the cerebral function. Other symptoms of encephalitis include fevers, headache, seizures, and focal neurologic deficits. Inflammation rarely confines itself to the meninges or parenchyma. As such, there is significant clinical overlap between these entities, termed “meningoencephalitis.” Nonetheless, the predominating features are useful for clinical distinction and treatment decisions.
Distinguishing viral from other causes of meningoencephalitis is challenging. History, exposures, imaging, and laboratory work are helpful in determining a cause. History and exposures for common entities are detailed later. Temporal lobe encephalitis on imaging is suggestive of a viral cause, particularly herpes simplex virus (HSV). Another useful clue is the finding of hydrocephalus, rarely seen with viral CNS infections.
Cerebrospinal fluid (CSF) analysis is the most important test for identifying a cause for CNS infections. The characteristic CSF profile for viral infection in lymphocyte-predominant leukocytosis (neutrophils may predominate very early in infection, but this will shift rapidly) is elevated protein less than 150 mg/dL, normal glucose concentration, and low to absent red blood cells (RBCs). Culture (the gold standard, but not always widely available) and molecular identification methods (e.g., polymerase chain reaction [PCR]) provide more definitive identification of the responsible pathogen.
Herpes Simplex Virus
Herpes simplex virus (HSV) is unique from other CNS viral infections in many ways. First, it is treated more easily with a readily available antiviral, acyclovir, making identification critical. Second, it is extremely common and demonstrates no seasonal predominance pattern and thus must be considered in all patients presenting with meningoencephalitis. Third, the clinical distinction between meningitis and encephalitis in this syndrome is clinically significant, because encephalitis can be fatal without treatment where meningitis is self-limited.
Encephalitis
Recognition and treatment of HSV encephalitis is critical. Without treatment, mortality approaches 70%, and even with treatment, mortality rates can be as high as 30%. Moreover, survivors frequently are left with neurologic and psychiatric sequelae.
Gender, exposures, geography, and timing are not useful in predicting which patients have HSV encephalitis. There is a well-described bimodal distribution with regard to age, with peaks occurring in children younger than age 20 and adults older than age 50, but any patient, regardless of age, should have CNS samples sent for HSV PCR if encephalitis is suspected.
Physical exam features are typical for encephalitis, including fever, altered mental status, focal deficits, and seizures. Oral lesions may or may not be seen. HSV-1 has a particular association with several behavioral syndromes, including hypomania, disinhibition (specifically the Klüver-Bucy syndrome), and amnesia, likely stemming from its predilection to affect the limbic system. Magnetic resonance imaging (MRI) demonstrating unilateral temporal lobe abnormalities supports the diagnosis, with or without mass effect. These findings are seen less commonly on CT. Treatment should be prompt to reduce sequelae of infection; Table 96.2 summarizes the dosing regimens. Initiation of therapy should not be delayed while awaiting confirmatory testing. Acyclovir infusion should be slow and with additional intravenous fluid boluses to prevent crystal formation and reduce risk of renal failure. Treatment should be 14 to 21 days in duration because of observed relapse in shorter courses of therapy. As of now this treatment is recommended to be parenteral throughout the duration of therapy.
TABLE 96.2
Treatment of Herpes Simplex Virus With Acyclovir
Data from Wilson JW, Estes LL. Mayo Clinic Antimicrobial Therapy Quick Guide : Oxford: University Press; 2011.
| CREATININE CLEARANCE >50 mL/min | CREATININE CLEARANCE 25–49 mL/min | CREATININE CLEARANCE 10–24 mL/min | CREATININE CLEARANCE <10 mL/min OR ANURIA | INTERMITTENT HEMODIALYSIS | CONTINUOUS RENAL REPLACEMENT THERAPY |
|---|---|---|---|---|---|
| 10 mg/kg IV q8h | 10 mg/kg IV q12h | 10 mg/kg IV q24h | 5 mg/kg IV q24h | 5 mg/kg IV q24h; on dialysis days, give after HD | 10 mg/kg IV q24h |
Weight is adjusted body weight for all calculations.
Meningitis
Although HSV-1 drives encephalitis, HSV-2 is associated more commonly with meningitis. The typical description of HSV meningitis is a recurrent infectious aseptic meningitis. Episodes of transient neurologic abnormalities associated with fever, headache, and meningitis may occur for 2 to 5 days at a time and spontaneously resolve. Incidence is lower than for HSV encephalitis, and demographic and seasonal features are difficult to determine. History, however, may elicit known genital herpes or lesions in a significant proportion of patients. Currently, a standardized guideline-based treatment approach to HSV meningitis does not exist. Initial treatment may be with acyclovir IV as described for encephalitis (see Table 96.2 ). However, after stability, these patients can be transitioned to oral therapy on discharge for 10 to 14 days of total acyclovir.
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