H1N1-associated Acute Respiratory Distress Syndrome Research Articles

Prone ventilation in H1N1 virus-associated severe acute respiratory distress syndrome: A case series.

Background:Management of H1N1 viral infection-associated acute respiratory distress syndrome (ARDS) has primarily been focused on lung protective ventilation strategies, despite that mortality remains high (up to 45%). Other measures to improve survival are prone position ventilation (PPV) and extracorporeal membrane oxygenation. There is scarcity of literature on the use of prone ventilation in H1N1-associated ARDS patients.Methods:In this retrospective study, all adult patients admitted to medical intensive care unit (ICU) with H1N1 viral pneumonia having severe ARDS and requiring prone ventilation as a rescue therapy for severe hypoxemia were reviewed. The patients were considered to turn prone if PaO2/FiO2 ratio was <100 cmH2O and PaCO2 was >45 cmH2O; if no progressive improvement was seen in PaO2/FiO2 over a period of 4 h, then patients were considered to turn back to supine. Measurements were obtained in supine (baseline) and PPV, after 30–60 min and then 4–6 hourly.Results:Eleven adult patients with severe ARDS were ventilated in prone position. Their age range was 26–59 years. The worst PaO2/FiO2 ratio range on the day of invasive ventilation was 48–100 (median 79). A total of 39 PPV sessions were done, with a range of 1–8 prone sessions per patient (median three sessions). Out of the 39 PPV sessions, PaO2/FiO2 ratio and PaCO2 responder were 38 (97.4%) and 27 (69.2%) sessions, respectively. The median ICU stay and mechanical ventilation days were 15 (range: 3–26) and 12 (range: 2–22) days, respectively. The common complication observed due to PPV was pressure ulcer. At ICU discharge, all except two patients survived.Conclusion:PPV improves oxygenation when started early with adequate duration and should be considered in all severe ARDS cases secondary to H1N1 viral infection.

Fifty Years of Research in ARDS. Is Extracorporeal Circulation the Future of Acute Respiratory Distress Syndrome Management?

Mechanical ventilation (MV) remains the cornerstone of acute respiratory distress syndrome (ARDS) management. It guarantees sufficient alveolar ventilation, high FiO2 concentration, and high positive end-expiratory pressure levels. However, experimental and clinical studies have accumulated, demonstrating that MV also contributes to the high mortality observed in patients with ARDS by creating ventilator-induced lung injury. Under these circumstances, extracorporeal lung support (ECLS) may be beneficial in two distinct clinical settings: to rescue patients from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV, and to replace MV and minimize/abolish the harmful effects of ventilator-induced lung injury. High extracorporeal blood flow venovenous extracorporeal membrane oxygenation (ECMO) may therefore rescue the sickest patients with ARDS from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV. Successful venovenous ECMO treatment in patients with extremely severe H1N1-associated ARDS and positive results of the CESAR trial have led to an exponential use of the technology in recent years. Alternatively, lower-flow extracorporeal CO2 removal devices may be used to reduce the intensity of MV (by reducing Vt from 6 to 3-4 ml/kg) and to minimize or even abolish the harmful effects of ventilator-induced lung injury if used as an alternative to conventional MV in nonintubated, nonsedated, and spontaneously breathing patients. Although conceptually very attractive, the use of ECLS in patients with ARDS remains controversial, and high-quality research is needed to further advance our knowledge in the field.

Cost analysis of miniaturized ECMO in H1N1-related ARDS managed by a single caregiver

Dear Editor, Extracorporeal membrane oxygenation (ECMO) has a significant impact on intensive care unit (ICU) patient costs. Human resources are a major cost driver for ECMO in severe acute respiratory distress syndrome (ARDS) [1]. However, recent developments in ECMO technology has allowed safe patient management by a single caregiver [2–4]. In the present report, we analyze the direct ICU costs of patients with influenza A (H1N1)-related ARDS supported with miniaturized ECMO systems and managed by a single caregiver. We performed an observational study of all patients (n = 10) with H1N1-associated ARDS treated with ECMO in Hospital S. Joao (Porto, Portugal), between November 2009 and April 2011. The clinical data and ECMO treatment details of this ICU patient cohort have been described in a previous report [5]. Patients were admitted in medical ICUs and managed by a single caregiver using miniaturized ECMO circuits (Rotaflow Centrifugal Pump plus Quadrox PLS and CARDIOHELP; Maquet Cardiopulmonary AG). In our single caregiver model, the ICU nurse primarily managed the ECMO patient under the coordination of 24/7 inhouse ICU physicians, with the backup of an on-call ECMO specialist. Our multidisciplinary ECMO specialist team (ICU physicians, ICU nurses, and cardiovascular perfusionists) is responsible for managing equipment and supplies, circuit preparation, patient transportation, troubleshooting, daily rounds, education, and service administration. Per patient ICU direct costs were analyzed retrospectively from clinical records and hospital databases using both top-down and bottom-up approaches. Bottom-up analysis was performed for all drugs, transfusion requirements, laboratory and imagiology exams. Regarding disposable items, bottom-up analysis was possible for ECMO-specific disposables and for renal replacement therapies. Costs with human resources were assessed using the top-down approach. Specific ECMO costs were also individualized for each ICU episode: (1) disposables devices; (2) laboratory tests; (3) transfusion requirements; and (4) drugs. The Ethics Committee of the Hospital S. Joao approved this study and waived the need for patients’ informed consent. Variables are reported as median and interquartile ranges, if not otherwise indicated. The cost drivers of H1N1-related ARDS patients treated with miniaturized ECMO are presented in Table 1. ECMO support corresponded to 63.6 (62.5–88.5) % of the ICU length of stay (LOS). The ICU LOS positively correlated (r = 0.97; p \ 0.001) with ICU patient costs [42,721 (33,358–56,801) €], but not with specific ECMO costs [r = 0.17; p = 0.63; 7,516 (5,599–7,736) €]. ECMO-specific costs represented 17.6 (13.1–18.1) % of the total ICU direct costs, mostly ECMO disposable devices [94.8 (87.1–96.1) %]. Daily ICU costs with antibiotics, sedation, analgesia and neuromuscular blockade, fluids and nutrition, vasoactive drugs, anticoagulation medications, and other unspecific drugs were higher during the period of ECMO support compared with the period without ECMO support. In conclusion, the use of miniaturized ECMO had a small impact on direct ICU costs in our cohort of H1N1-related severe ARDS patients managed by a single caregiver and did not correlate with the ICU LOS. Knowledge of the incremental costs associated with miniaturized ECMO will contribute to the clarification of its cost-effectiveness in severe ARDS.

Extracorporeal Membrane Oxygenation for Pandemic Influenza A(H1N1)–induced Acute Respiratory Distress Syndrome

Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy. To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality. Data from patients admitted for H1N1-associated ARDS to French ICUs were prospectively collected from 2009 to 2011 through the national REVA registry. We analyzed factors associated with in-ICU death in ECMO recipients, and the potential benefit of ECMO using a propensity score-matched (1:1) cohort analysis. A total of 123 patients received ECMO. By multivariate analysis, increasing values of age, lactate, and plateau pressure under ECMO were associated with death. Of 103 patients receiving ECMO during the first week of mechanical ventilation, 52 could be matched to non-ECMO patients of comparable severity, using a one-to-one matching and using control subjects only once. Mortality did not differ between the two matched cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32). Interestingly, the 51 ECMO patients who could not be matched were younger, had lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01). Under ECMO, an ultraprotective ventilation strategy minimizing plateau pressure may be required to improve outcome. When patients with severe influenza A(H1N1)-related ARDS treated with ECMO were compared with conventionally treated patients, no difference in mortality rates existed. The unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a lower mortality.

Portable miniaturized extracorporeal membrane oxygenation systems for H1N1-related severe acute respiratory distress syndrome: A case series

BackgroundTechnological advances improved the practice of “modern” extracorporeal membrane oxygenation (ECMO). In the present report, we describe the experience of a referral ECMO center using portable miniaturized ECMO systems for H1N1-related severe acute respiratory distress syndrome (ARDS). MethodsAn observational study of all patients with H1N1-associated ARDS treated with ECMO in Hospital S. João (Porto, Portugal) between November 2009 and April 2011 was performed. Extracorporeal membrane oxygenation support was established using either ELS or Cardiohelp systems (Maquet-Cardiopulmonary-AG, Hirrlingen, Germany). ResultsTen adult patients with severe ARDS secondary to H1N1 infection (Pao2/fraction of inspired oxygen, 69 mm Hg [56-84]; Murray score, 3.5 [3.5-3.8]) were included, and 60% survived to hospital discharge. Five patients were uneventfully transferred on ECMO from referring hospitals to our center by ambulance. Six patients were treated during the first postpandemic influenza season. All patients were treated with oseltamivir, and 1 received in addition zanamivir. Four patients received corticosteroids. Nosocomial infection was the most common complication (40%). Of the 4 deaths, 2 were caused by hemorrhagic shock; 1, by irreversible multiple organ failure; and 1, by refractory septic shock. ConclusionIn our experience, ECMO support was a valuable therapeutic option for H1N1-related severe ARDS. The use of portable miniaturized systems allowed urgent rescue of patients from referring hospitals and safe interhospital and intrahospital transport during ECMO support.

Cerebral edema and a transtentorial brain herniation syndrome associated with pandemic swine influenza A (H1N1) virus infection

Acute encephalitis, encephalopathy, and seizures are known rare neurologic sequelae of respiratory tract infection with seasonal influenza A and B virus, but the neurological complications of the pandemic 2009 swine influenza A (H1N1) virus, particularly in adults, are ill-defined. We document two young adults suffering from H1N1-associated acute respiratory distress syndrome and renal failure who developed cerebral edema. The patients acutely developed a transtentorial brain herniation syndrome including a unilateral third nerve palsy (dilated and unresponsive pupils), elevated intracranial pressure, coma, and radiological evidence of diffuse cerebral edema. In both patients, neurological deterioration occurred in the context of hyponatremia and a systemic inflammatory state. These patients illustrate that severe neurologic complications, including malignant cerebral edema, can occur in adults infected with H1N1 virus, and illustrate the need for close neurological monitoring of potential neurological morbidities in future pandemics.

Use of Inhaled Epoprostenol in Patients with H1N1 Influenza-Associated Acute Respiratory Distress Syndrome: A Case Series

To report a series of patients with confirmed novel influenza A (H1N1) and refractory hypoxemia secondary to acute respiratory distress syndrome (ARDS) treated with inhaled epoprostenol. Four patients admitted to our institution with confirmed H1N1 and refractory hypoxemia were treated with inhaled epoprostenol as potential salvage therapy. All patients were treated initially with antimicrobial agents, followed by oral oseltamivir at the time of suspicion or confirmation of H1N1. None of the patients received intravenous peramivir or extracorporeal membrane oxygenation. Clinically significant improvement in oxygenation was seen in only 1 of the patients receiving inhaled epoprostenol. Mortality was significant, with only 1 patient discharged from the hospital. Use of inhaled epoprostenol for the treatment of hypoxemia secondary to ARDS has been reported, with conflicting results. Deliveries via the inhalational route compared to the intravenous route theoretically preferentially vasodilate well-ventilated areas of the pulmonary vasculature, improving arterial oxygenation and pulmonary gas exchange. Increase in the ratio of arterial oxygen tension to fraction of inhaled oxygen is greatest upon initiation of inhaled epoprostenol, but this benefit has not been conclusively demonstrated to persist throughout therapy. Serious H1N1 presents a unique challenge for clinicians, often requiring the use of salvage therapies to treat critically ill patients. Given the variable response to treatment, it remains unclear whether inhaled epoprostenol is beneficial in H1N1-associated ARDS. Identification of patients for whom this therapy is most appropriate remains a clinical challenge.

Severe H1N1-Associated Acute Respiratory Distress Syndrome: A Case Series

Background Acute respiratory distress syndrome resulting from novel influenza A virus (H1N1) infection remains uncommon. Methods We describe the clinical profiles of adult patients with acute respiratory distress syndrome due to microbiologically confirmed H1N1 admitted to a medical intensive care unit in San Francisco, California over a 2-month period. Results Between June 1 and July 31, 2009, 7 patients (age range: 25-66 years; 4 patients under the age of 40 years; 6 male; 1 pregnant) were diagnosed with H1N1, with 5 of 6 (83%) having initial false-negative rapid testing. All developed respiratory failure complicated by acute respiratory distress syndrome, with 4 additionally developing multiorgan dysfunction. All were managed with a lung protective ventilator strategy (average number of days on the ventilator: 16), and 4 patients also required additional rescue therapies for refractory hypoxemia, including very high positive end-expiratory pressure, inhaled epoprostenol, recruitment maneuvers, and prone positioning. Despite these measures, 3 patients (43%) ultimately died. Conclusions Clinicians should be vigilant for the potential of H1N1 infection to progress to severe acute respiratory distress syndrome in a variety of patient demographics, including younger patients without baseline cardiopulmonary disease. A high degree of suspicion is critical, especially with the relative insensitivity of rapid testing, and should prompt empiric antiviral therapy.