Case Study
A previously well 32-year-old woman presented to the Emergency Department at 37 weeks’ gestation with a two-day history of cough, fever, and general malaise; an increase in shortness of breath had prompted her to come to hospital.
On arrival, she was dyspneic with oxygen saturation of 88 percent on room air and grossly tachypoeic. Despite the administration of 15 liters of oxygen via a facemask, she remained hypoxemic (PaO2 = 60 mmHg/8 kPa). She was tachycardic but normotensive and pyrexial. Her temperature was measured as 38.3℃. Chest radiography showed right lower lobe infiltrates. A nasopharyngeal swab was taken and subsequently confirmed the presence of H1N1 influenza A virus (RT-PCR test); co-amoxiclav, clarithromycin, and oseltamivir (Tamiflu) were started.
While being assessed in the Emergency Department, the patient’s condition deteriorated rapidly, with worsening respiratory distress, hypoxia, and tachycardia. Cardiotocography identified fetal distress requiring an emergency cesarean delivery. The procedure was performed under general anesthesia following a rapid-sequence induction. Invasive monitoring was started, including arterial and central pressure monitoring. Following delivery, the patient remained sedated and ventilated owing to her high oxygen requirements and was transferred to the ICU.
Despite controlled ventilation with high inspiratory oxygen fractions (FiO2 = 0.9), her oxygenation could not be improved (PaO2 = 45 mmHg/6 kPa). A second chest radiograph showed bilateral infiltrates consistent with acute respiratory distress syndrome (ARDS). The patient also rapidly developed signs of distributive shock and renal failure, for which she was treated with vasopressors (norepinephrine and vasopressin) and renal replacement therapy (continuous venovenous diahemofiltration [CVVDH]). A trial of high-frequency oscillation ventilation (HFOV) was started, and over a period of 72 hours the patient’s respiratory condition improved; conventional ventilation with low tidal volumes (6 ml/kg of body weight) was reinstated after another 48 hours. Her condition continued to improve, and a week after her admission to the Emergency Department, she was able to be extubated and discharged to normal ward care.
Key Points
Pregnant women who are infected with H1N1 influenza A and show signs of acute respiratory distress or failure can deteriorate rapidly and may require ventilation and delivery of the premature fetus.
Antiviral agents should be administered as soon as influenza is suspected.
Appropriate timing of delivery needs to be determined by a multidisciplinary team of senior clinicians.
Prompt and aggressive intensive care therapy with appropriate organ support should be instigated as soon as indicated.
Influenza poses significant risk for pregnant women and their fetuses, and pregnant women should therefore be offered the seasonal and specific vaccines.
Discussion
Influenza is an RNA virus that is classified into either A, B, or C types; types A and B infect humans and are known to cause seasonal epidemics. Type A can also cause pandemics. Influenza A is characterized by its surface antigens: hemagglutinin (H) and neuraminidase (N). The different types of the surface antigens (e.g., H1, H2, N1, N2) are used to describe the subtype of the influenza A virus. These two surface antigens may undergo mutations, causing antigenic drift. It is this process that requires the annual modifications of the vaccine.1
Pregnant women who are infected with the H1N1 virus carry an increased risk of morbidity and mortality from pandemic influenza. This chapter focuses on the results of the pandemic caused by the influenza A subtype H1N1 in 2009–10.
Women are at higher risk of contracting the H1N1 virus and developing a severe respiratory infection through the antenatal period and for up to 2 weeks following delivery. A UK study from the pandemic in 2009 showed that pregnant women with H1N1 were three times more likely to be admitted to hospital than nonpregnant women.2 Similar data from the United States show that pregnant women were four times more likely than the general population to be admitted if infected with H1N1.3
Pregnant women are at higher risk from viral infections due to pregnancy-related physiologic and immunologic changes. Increased heart rate and oxygen consumption and decreased lung capacity all lead to decreased cardiovascular reserve. Pregnant women have a lower oncotic pressure, which may predispose them to a higher risk of pulmonary edema and respiratory compromise. There is a decrease in cell-mediated immunity with normal levels of humoral immunity.4 It is the T-helper cells of the cell-mediated immune system that facilitate the apoptosis of host cells infected with a virus.
The influenza vaccine is an inactivated vaccine, which may be mono- or multivalent. The inactivated pathogens provide prophylactic protection against the virus by eliciting both antibodies and cytotoxic T-lymphocytes.5 The inactivation of the pathogen by either chemical exposure or heat denaturation renders the virus dead and noninfectious; it is therefore safe in pregnancy.5 The valency of the vaccine describes the number of antigens to which the vaccine will convey immunity. A monovalent vaccine is a vaccine against a single strain (e.g., H1N1), whereas a multivalent vaccine will provide immunity against two or more strains of the same microorganism.5 For example, the influenza vaccine may contain both the seasonal and pandemic strain of influenza.
The influenza vaccine is considered to be safe in pregnancy and provides excellent protection to both mother and fetus. It should be offered to all pregnant women.6
Presentation
The presentation of H1N1 consists of (in order of frequency) fever, cough, breathlessness, headache, sore throat, and nausea and vomiting.2 Clinical signs include tachycardia, tachypnea, fever > 38°C, oxygen saturations < 94 percent on room air, and systolic hypotension.2 Pregnant women are more likely to present with dyspnea as the predominant symptom.3 One study has shown that the independent prognostic indicators for the severity of infection were levels of C-reactive protein (CRP) greater than 100 mg/liter and radiologic signs of pneumonia.2 Patients may go on to develop ARDS and multiorgan failure, requiring higher levels of intensive care therapy.
Management
Once an infection with H1N1 virus or other types of influenza is suspected, a rapid and coordinated approach of different senior specialists is mandatory. The examination of the woman should be initiated with an assessment of the patient’s airway, breathing, and circulation (ABC), keeping in mind that resuscitation of the mother is very likely to also improve the fetal condition. Adequate maternal oxygenation and ventilation, as well as a sufficient blood pressure, should be key goals in the initial resuscitation phase. It is important to appreciate the physiologic changes in pregnancy when managing the critically ill parturient. For example, the higher partial pressure of oxygen in the blood usually seen in pregnancy must be maintained to provide adequate oxygenation of the mother and the fetus. It cannot be overstated that aggressive management of the mother is the best way to improve fetal outcome.
Diagnosis
All women should be tested as soon as an infection with influenza is suspected. A rapid antigen test is available and will produce results within 30 minutes. This test has been shown to have a false-positive rate of 38 percent.7 However, any woman with suspected pandemic influenza should be managed as if infected until a RT-PCR test (results 6–10 hours) or viral cultures (results 3–10 days) prove otherwise.8
Treatment
Oseltamivir (Tamiflu) and zanamivir (Relenza) are neuraminidase inhibitors that are used for the treatment of influenza. Treatment duration is usually between 5 and 10 days depending on the severity of disease. Zanamivir is an inhaled drug and is contraindicated in chronic respiratory disease because it may cause bronchospasm.9 A meta-analysis has shown that oseltamivir reduces the time of clinical symptoms as well as the incidence of lower respiratory tract complications and hospital admissions.10
Antiviral drugs work best when given as close as possible to the onset of symptoms (or at least within the first 48 hours of the onset of symptoms). Early administration of antiviral drugs after admission to hospital for presumed influenza can prevent respiratory failure and death.11
Infection Control Guidance
The Centers for Disease Control and Prevention in the United States has issued infection control guidance for the management of pregnant or peripartum patients. They recommend:12
All suspected or confirmed cases must be managed in isolation rooms.
Standard precautions must be taken using gloves, gowns, and hand hygiene.
Respiratory hygiene and cough etiquette are necessary (education, cover mouth and nose on sneezing).
Hand hygiene after contact with respiratory secretions is required.
Droplet precautions (facemask) are required.
Spatial separation of patients who are febrile with respiratory illness is necessary.
These precautions should be continued for 7 days after the onset of the illness or 24 hours since last symptoms (fever, respiratory symptoms).
Following delivery, the mother and baby should be separated until the mother:
Has received 48 hours of antiviral treatment,
Has been apyrexial for 24 hours (without antipyretics), and
Is able to control her cough and respiratory secretions.
For local implementation of these guidelines, close cooperation with the microbiology and/or infection control team is paramount.
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