Critical care services in the H1N1 2009 influenza pandemic – the present status and preparing for an increasing demand

While countries like the USA, Mexico, Australia and New Zealand have already experienced the first marked peaks of H1N1 2009 influenza pandemic, the fast approaching winter season for Europe presages the necessity of facing the similar challenge. Pressures on critical care[1] are already building up and some EU countries have already made plans to significantly increase that capacity for example for ventilating patients. Reports on epidemiological and clinical presentation of influenza pandemic can provide estimates of the burden of disease. Studies on effectiveness of treatment, use of public health resources, and outcomes for patients give vital lesson for countries which have yet to be significantly affected. Recently WHO held a global consultation to gather information about the clinical features and management of this specific pandemic influenza which drew on the findings and experiences presented by around 100 clinicians, scientists, and public health professionals from the Americas, Europe, Asia, Africa, the Middle East and Oceania. Some initial findings have been made public by WHO.[i]

In addition a range of recently published studies on epidemiological and clinical presentations of the A(H1N1) influenza pandemic and their impact on critical care services is presented below.

Critical Care Services and 2009 H1N1 Influenza in Australia and New Zealand
The ANZIC Influenza Investigators
NEJM, October 8, 2009 (10.1056/NEJMoa0908481)

In this inception-cohort study the authors presented demographic and clinical characteristics of the A(H1N1) influenza infected patients, along with calculation per million inhabitants of the numbers of ICU admissions, bed-days, and days of mechanical ventilation due to influenza infection in all intensive care units (ICUs) during the 2009 winter. The authors found that the number of ICU admissions due to influenza A in 2009 was 15 times the number due to viral pneumonitis in recent years. Infants (0 to 1 y.o.) and adults (25 to 64 y.o.) were identified as on particular risk, and pregnant women, adults with a BMI over 35, and indigenous Australian and New Zealand populations also appeared to have an increased risk. In-hospital mortality exceeded 16%.

Critically Ill Patients With 2009 Influenza A(H1N1) in Mexico
Guillermo Domínguez-Cherit, Stephen E. Lapinsky, Alejandro E. Macias, Ruxandra Pinto, Lourdes Espinosa-Perez, Alethse de la Torre et al.
JAMA. 2009;302(17):(doi:10.1001/jama.2009.1536).

The retrospective observational study describes the epidemiological characteristics, comorbidity, illness progression, treatments, and clinical outcomes of 58 critically ill patients with  influenza A(H1N1) 2009 in Mexico from March 24 to June 1, 2009. The outcomes of this study indicated that the first series of Mexican cases had similar demographic and clinical presentation as in the other affected countries however mortality rate was higher. One explanation was that early medical intervention and prompt clinical treatment may mitigate the severity of illness and reduce mortality.

Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada
Anand Kumar, Ryan Zarychanski, Ruxandra Pinto, Deborah J. Cook, John Marshall et al.
JAMA. 2009;302(17):(doi:10.1001/jama.2009.1496).

The prospective observational study describes the epidemiological characteristics, clinical features, treatments, and outcomes of 168 critically ill patients infected with 2009 influenza A(H1N1) in Canada from April 16 to August 12, 2009. The report showed that critical illness due to influenza A(H1N1) 2009 predominantly affected young patients with few major comorbidities and was associated with severe hypoxemic respiratory failure, often requiring prolonged mechanical ventilation and rescue therapies.

Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009
Seema Jain, Laurie Kamimoto, Anna M. Bramley, Ann M. Schmitz, Stephen R. Benoit et al.
NEJM, October 8, 2009 (10.1056/NEJMoa0906695)

This report by CDC investigators describes the clinical characteristics of the earliest 272 patients hospitalized with the 2009 H1N1 virus in the United States. Seventy-three percent of the patients had at least one underlying medical condition including asthma; diabetes; heart, lung, and neurologic diseases; and pregnancy. Forty-five percent of patients were obese or morbidly obese, however most of them (81%) had an accompanying underlying condition. Hence obesity did not seem to be an individual risk factor for severe influenza disease. Data from this study suggest that the use of antiviral drugs was beneficial, especially when initiated early.

Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome
The Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators
JAMA. 2009;302(17):(doi:10.1001/jama.2009.1535).

This study presents the characteristics of 68 patients with pandemic A(H1N1)  influenza associated acute respiratory distress syndrome (ARDS) treated with extracorporeal membrane oxygenation (ECMO) in ICUs  between June 1 and August 31, 2009. The analysed cases were often young adults, pregnant or postpartum, obese, had severe respiratory failure before prolonged mechanical ventilation and ECMO therapy. At the end of the observation period 48 of the 68 patients (71%) had survived to ICU discharge, of whom 32 had survived to hospital discharge and 16 remained as hospital inpatients. Fourteen patients (21%) had died and 6 remained in the ICU, 2 of whom were still receiving ECMO.

Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain
Rello J., Rodríguez A., Ibañez P., Socias L., Cebrian J., Marques A et. al.
Crital Care, 2009 Sep 11;13(5):R148

This study presents one of the first reports of  intensive care use during the H1N1 2009 influenza pandemic in Europe. Rello J. and his group presents the clinical and epidemiologic characteristics of the first 32 A(H1N1) 2009 laboratory confirmed cases admitted to the intensive care use (ICU)  in Spain. In the analysed group (25% children and 75% adults) the median age was 36 (IQR=31-52) where 10 (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbated chronic obstructive pulmonary disease (CODP) and 1 (3.1%) secondary bacterial pneumonia (with streptococcus bact.) Twenty-four patients (75.0%) developed multiorgan dysfunction, 24 (75.0%) required mechanical ventilation and 7 (21.9%) received renal replacement techniques due to renal failure. Six patients died within 28 days and there were two additional late deaths.

All patients received presumptive antibiotic therapy. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received double-dose (300 mg/day), the duration of treatment ranged from 5 to 10 days. The clinical data suggests that early oxygen therapy and oseltamivir treatment play important role in the treatment for severe A(H1N1)v influenza infections.

Modelling the impact of an influenza A/H1N1 pandemic on critical care demand from early pathogenicity data: the case for sentinel reporting
Ercole A., Taylor., B.L., Rhodes A., Menon D.K.,
Anaesthesia, 2009 Sep;64(9):937-41. Epub 2009 Jul 23

While most of the countries worldwide prepared pre-pandemic plans including modelling and forecasting work, the most accurate method for estimating real burden of pandemic is to base it on current statistics taking into account present public health approach. This study attempts to quantify the potential critical care burden of influenza A/H1N1 in a European  population (England) using the CDC FLUSURGE 2.0 model based on data on disease severity from the USA and Mexico. Estimates were presented using data from the UK Office for National Statistics; the total number of adult level 3 beds of 2030, the total paediatric intensive care beds of 265, the total number of available ventilators was assumed to be equal to the number of critical care beds. The total number of confirmed cases of influenza A/H1N1 in England at the time of writing was 6162, which number was the starting point of analysis. The duration of pandemic was assumed as 12 weeks. The model found that when none of the first 6162 confirmed cases had been admitted to hospital, 95% confidence limit on admission rates led to a range in predicted peak critical care bed occupancy of between 0% and 37% of total capacity, with peak ventilator usage ranging between 0% and 19% of total capacity. For hospital admission rates above 0.25% the model critical care bed availability would be exceeded. Considering the fact that only 10% of critical care beds in England are in specialist paediatric units and 30% of estimated patients requiring critical care will be children, paediatric intensive care facilities are likely to be quickly exhausted and the authors suggest that older children should be managed in adult critical care units. This study shows that data from sentinel reporting systems and up-to-date modelling allow for real-time forecasting which is critically useful in the decision-making process.

ECDC comment (30^th October 2009)

These recent studies confirm prior observations that while healthcare services in a number of countries affected by the first pandemic (H1N1) 2009 wave coped reasonably well with the increased workload the greatest pressures were on intensive care units and specifically concerning assisted ventilation capacity. The findings from the recent WHO consultation on the clinical aspects of the pandemic support these conclusions.

After a moderate first pandemic wave in some Western European countries, the pandemic is now establishing itself across Europe and critical care services are being put under considerable pressure. EU/ EEA Member States are adopting various strategies to effectively deal with these pressures. For example, early access to antiviral treatment has been facilitated by providing prescriptions through a telephone service, as was done in the UK or relaxing the prescriptions requirements, as was done in Norway recently. When adopting these strategies, special care is being given and should be given to differential diagnosis and identifying severe bacterial infections, including meningococcal meningitis cases.

The published case series highlight the rapid progression of the severity of illness in a small subset of patients infected by influenza (H1N1)v. Rapid access of critically ill patients to advanced treatment is key to improving survival rates and efforts should be made to shorten time delays in triaging, assessing and referring critically ill patients. WHO has recently published revised guidelines for the clinical management of pandemic influenza patients, and these guidelines also include triaging algorithms for resource-limited settings. Identifying high-risk patients and patients with severe or progressing disease is the cornerstone of these algorithms.[ii]

In affected countries, workload in intensive care units has been very high partly due to the fact that many pandemic influenza patients need invasive mechanical ventilation for extended periods of time. Personnel resources, equipment, supplies and medications all are affected in this situation. However, the local pandemic waves tend to be shorter in duration than when seen from the national perspective and Member States are sometimes considering the possibility to share resources across administrative borders. Recent successful examples include referrals of patients across country borders for Extra Corporeal Membrane Oxygenation (ECMO).

Sharing of clinical experiences and lessons learned at the local level would greatly benefit the countries in the acceleration phase of the first pandemic wave right now.