Unit 8 H1n1

Thursday, February 10, 2022 4:04:17 PM

Unit 8 H1n1



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The H1N1 influenza virus infection in very young infants appears to be mild to moderate in severity. The outcomes of the infants may be influenced by antiviral therapy. Treatment with antiviral oseltamivir appears to have no major adverse effects. Swine influenza A H1N1 virus is a cause of pandemic acute respiratory tract infection among children and adults that was first reported in Mexico and the Southwestern United States in March Thereafter, infection with this virus has been reported in almost every country [ 8 , 10 , 20 , 22 ]. The spectrum of the disease varies from mild upper respiratory symptoms to severe lower respiratory tract disease with respiratory failure. Despite the rapid spread of the pandemic influenza A virus, most cases did not have a serious course of disease [ 5 , 6 ].

However, mortality due to pandemic H1N1 influenza has also been reported [ 21 ]. Hospitalization rates are highest for children under the age of 5 years, especially those under the age of 1 year. Because influenza viruses rarely infect very young infants, pandemic planning has focused on adults and older children [ 13 , 17 , 23 ]. Since few reports are available on pandemic H1N1 influenza infection in infants, the objective of this study was to examine the clinical characteristics and management of the disease in very young infants. We also wish to share our clinical experiences on this pandemic H1N1 infection of infants. However, a later pandemic may be different in clinical presentation. This study included ten infants diagnosed with H1N1 influenza virus infection during the outbreak season, between October and December , peak period for central Anatolia, in the neonatal intensive care unit NICU of Dr.

Sami Ulus Maternity and Children's Hospital. All infants diagnosed with community-acquired H1N1 virus infection were included in this observational study. The clinical data, results of laboratory testing and radiological studies, medication administered, and the outcomes of the patients were recorded. For prevention of transmission within the NICU, in addition to the standard measures, patients were isolated during the hospitalization period and kept under observation in incubators. Although our unit is a family-based care unit, no mothers having any influenza like symptoms were allowed to enter the NICU. Breast milk policy was continued during the clinical course.

Standard surgical masks, non-sterile gloves, and gowns were used while handling the babies. Other methods, such as negative pressure isolation for the reduction of virus transmission in hospital, were not used. Other patients in the NICU having any symptoms consistent with nosocomial infection during this period were also investigated for nosocomial H1N1 virus infection. Routine laboratory studies e. The diagnosis of swine H1N1 infection was confirmed by testing of respiratory samples nasopharyngeal and pharyngeal swabs with pandemic H1N1 influenza specific real-time PCR assay. Statistical analyses were performed using SPSS All infants including the preterms were admitted from home.

H1N1 influenza virus infections in these patients did not originate from a peri- or prenatal infection of the mother. The youngest was a 5-day-old boy. Age on admission, birth-weight, and gestational age of the patients are shown in Table 1. Apnea was the initial symptom in three patients. No patient had the symptom of diarrhea, but there was vomiting in one patient. Mean duration of the fever was 2. While a cough was present in only five patients on admission, the additional two patients developed it during their clinical course. Two patients required oxygen support case 1 and 3. Case 3 had been mechanically ventilated for 2 days.

The co-morbid conditions, gastro-esophageal reflux, and patent ductus arteriosus were present in case 3. Case 10 was a 5-day-old full-term infant who presented with fever and maculopapular rash. Case 3 and case 5 also had co-infection Table 1. No nosocomial H1N1 infections were determined during this period. The mean duration of hospitalization was 7. Demographic features and clinical findings are summarized in Table 1. An elevated CRP level was encountered only in case 3 whose Klebsiella pneumoniae was isolated from his tracheal aspirate. His chest radiography revealed diffuse infiltrates on both lung fields.

Arterial blood gas analyses were normal in all except two patients with mild hypoxemia. No organ dysfunction was noted in any subject. On chest radiography, there were radio-opacities on both lung fields in six patients Fig. Laboratory findings are summarized in Table 1. Note diffuse radio-opacities on both lung fields on chest radiography of case 5 obtained at second day of hospitalization. All patients with proven H1N1 infection were given oseltamivir medication in addition to supportive care. Empiric antibiotic treatment was provided to all patients until the first culture results were obtained. In addition, the patients with co-infection received specific antimicrobial therapy.

Recovery was obtained in all patients with no residual deficits. No adverse effects of the antiviral oseltamivir treatment, e. There are few reports on the effects of previous influenza pandemics , , and on infants. Although influenza rarely causes illness in newborns and very young infants, we know that in pandemic, infant mortality and preterm delivery was increased [ 24 ], but this occurred before the development of modern neonatal intensive care and antiviral and antimicrobial therapy. In our cases, clinical course was mild to moderate in severity and there was no mortality.

Nevertheless, there are also reports of severe cases in preterm infants during epidemics, which developed significant lung injury [ 2 , 7 , 11 , 16 , 27 ]. This is likely to be related to the immature immune function of preterm infants. In our study, of the three preterm infants, only one case 3 had a severe clinical picture that necessitated intubation and mechanical ventilation. This may be associated with his co-morbid clinical conditions. The course of the disease in neonates and young infants seems to have some differences when compared with that in other age groups. Symptoms of H1N1 infection in very young infants are not specific in comparison with those in older patients.

Very young infants can present without fever but with other non-specific symptoms like apnea. This may be because of the low level of immunity in neonates. As with the present cases, apnea may be the major symptom. Barak et al. Clinicians should therefore be aware of insidious symptoms or signs of the probable infection in infants during a pandemic. Illnesses caused by influenza virus infection are difficult to distinguish from illnesses caused by other respiratory pathogens based on symptoms alone. In addition, young children are less likely to have typical influenza symptoms e.

Infants may present with fever and lethargy, indistinguishable from bacterial sepsis, but may not have cough or other respiratory symptoms or signs [ 28 ]. In our series, although diarrhea was not present in any patient, there was vomiting in one patient. It is not possible to compare our results with other series because no other series of very young infants has yet been published. As was observed in our own cases, in cases with H1N1 infection, radiographic findings commonly include diffuse mixed interstitial and alveolar infiltrates, although lobar and multi-lobar distributions occur, particularly in patients with bacterial co-infection.

On chest computed tomography images, multiple areas of ground-glass opacities, air bronchograms, and alveolar consolidation, particularly in the lower lobes, are seen [ 15 ]. In addition, small pleural effusions may occur in these patients, but this may be due to volume overload or possibly to empyema [ 30 ]. Children less than 1 year old are also known from previous pandemics to be at increased risk of complications [ 1 ].

As with our cases, the outcomes of these infants may have been influenced by antiviral oseltamivir therapy. Although use of oseltamivir in children less than 1 year old with novel H1N1 infection was approved by the FDA for the pandemic period and the recommended dosage is age-based [ 18 ], there is limited data on the safety of oseltamivir or zanamivir in this age group. Treatment of seasonal influenza in children less than 1 year old suggests that severe adverse events related to oseltamivir are rare [ 26 ]. Although all of our patients received oseltamivir treatment, no adverse effects were seen in any patient. WHO suggests the use of a simple medical mask when working within a distance of 1 m from a patient with suspected H1N1 infection.

Although the United States Centers for Disease Control and Prevention recommends N95 masks, their use is not universal in all countries. Influenza viruses are primarily spread from person to person by respiratory droplets. Random-effect pooled estimates, albeit limited by underlying heterogeneity, suggested an overall in-hospital mortality of Forest plot for the risk of mortality. Accordingly, this treatment may represent a promising alternative to standard protective ventilation.

Nonetheless, short-term survival can be further improved, most likely by refinements in ancillary therapy and means of mechanical ventilation. The H1N1 influenza pandemic has generated a plethora of research efforts, focusing on prevention, diagnosis and treatment [ 19 ]. Indeed, such efforts have been largely justified by the substantial risk of death even in young and apparently healthy subjects developing fulminant ARDS [ 1 , 20 ]. Given these premises, the application of current state-of-the-art ECMO technologies has been proposed as a promising means to reduce the morbidity and mortality of ARDS, complicating suspected or confirmed H1N1 influenza [ 2 , 21 ].

Despite the availability of several recent studies focusing on the risk-benefit balance of ECMO in this setting, the vast majority of such publications are case reports or very small series. Even larger studies have usually a single center or single country setting, and thus have limited external validity. Given the superior statistical power and external validity of systematic reviews, our work provides important insights on the clinical role of ECMO in the context of H1N1 infection complicated by ALI. Indeed, ECMO usage is feasible in this clinical setting, as testified by the now large number of patients who have successfully received this treatment, have been maintained on ECMO for several days and have obtained a final satisfactory clinical outcome.

Thus, ECMO implementation in this type of patients can be recommended in selected centers provided training, logistics and resources are adequate. Apparently, the positive results reported by the included studies stemming from several international tertiary care centers may be due to the short period median of two days occurring between the start of mechanical ventilation and the start of ECMO, the elevated standards of the clinical centers that performed ECMO, as suggested by the high referral rate, and the young age of the treated patients median 35 years. However, further studies are required to confirm or disprove the importance of these patient and procedural factors to achieve favorable clinical results with ECMO in ALI due to H1N1 infection.

Quoting verbatim the Extracorporeal Life Support Organization, the main indications for ECMO are acute severe heart or lung failure with high mortality risk despite optimal conventional therapy [ 22 ]. Severity of illness and mortality risk should be appraised as precisely as possible using measurements for the appropriate age group and organ failure. Most contraindications are relative, balancing the risks of the procedure including the risk of using valuable resources which could be employed for others versus the potential benefits. The relative contraindications are: 1 conditions incompatible with normal life if the patient recovers; 2 preexisting conditions which affect the quality of life central nervous system status, end stage malignancy, risk of systemic bleeding with anticoagulation ; 3 age and size of the patient; and 4 futility: patients who are too sick, have been on conventional therapy too long or have a fatal diagnosis.

The application of these guidelines in the context of ARDS is jeopardized by the lack of clear principles for selecting the venous-venous versus the venous-arterial configuration [ 22 ]. Data in the literature are scarce, but a careful revision of the patient population included in this systematic review depicts a cohort of ARDS patients suffering from severe circulatory failure and organ dysfunction or in need of supramaximal inotropic support to maintain hemodynamic stability. Accordingly, the care of these patients still requires significant improvement.

There are also institutional issues that need to be addressed as the treatment of these patients is variable in terms of allocation general versus cardiothoracic intensive care units and specialists who are caring for them intensive care unit specialists versus cardiac surgeons. These differences necessarily bias the trends and attitudes in clinical management. We formally tried to explore the impact of veno-arterial versus veno-venous ECMO by means of meta-regression, given that the latter is usually associated with fewer vascular complications, but may provide inadequate hemodynamic support and less blood oxygenation in comparison to veno-arterial ECMO.

On the other side, veno-arterial ECMO is much more invasive in terms of vascular access, risk of bleeding and may produce harlequin syndrome that is, loco-regional and asymmetric discrepancies in blood flow distribution appearing as differences in skin color, sweating and temperature. However, we did not find statistical evidence for a difference between these two means to establish ECMO. Despite the small number of patients, which has prevented its inclusion in our meta-analysis, Roch and co-workers reported a series of nine patients treated with ECMO at a single institution for H1N1 ARDS.

Among them, six were treated with veno-venous and three with veno-arterial ECMO. Baseline respiratory parameters were not different between the two groups and both benefited immediately from the extracorporeal support in terms of gas exchange; whereas there was a striking difference among survivors and non-survivors in terms of the hemodynamic effects of ECMO: patients who died had no improvement of circulatory function, as defined as increased requirements or inability to wean from inotropic agents or increased lactates [ 23 ]. The most recent case series included in this systematic review is very promising [ 16 ]. This work has several limitations, including all those typical of systematic reviews and meta-analyses.

Moreover, pooling observational studies, this review cannot overcome the limitations of primary studies, which were of relatively high quality, but still none was based on randomized allocation [ 26 ]. Indeed, only meta-analyses of homogeneous randomized trials should be considered the final scientific proof of the efficacy and safety of any medical intervention. However, systematic reviews and meta-analyses of non-randomized studies can be meaningful and guide clinical research and practice, even if only by emphasizing the limitations of the available clinical evidence.

This meta-analysis is also not powerful enough to define the exact role of different types of ECMO. Furthermore, the exclusion of more than 70 reports because including less than 10 cases clearly calls for more collaborative research efforts. This type of collaboration is essential for present and future clinical challenges resembling the H1N1 pandemic. If only a fraction of these separate case series were to be combined, we would have achieved much greater statistical power and precision. In addition, we did not formally appraise agreement between reviewers before final consensus for study search, selection, abstraction or appraisal.

Finally, no cases of H1N1 outbreaks have been reported recently, and thus the main strength of the present work is to prove that the experience with ECMO for ALI due to H1N1 infection, given its favorable effects on younger and previously healthier patients, may be helpful in the future in similar situations. Despite this, prolonged support more than one week is required in most cases, and subjects with severe comorbidities or multi-organ failure remain at high risk of in-hospital death. Eight case series with at least 10 patients each have been published so far describing the use of ECMO in patients with ALI due to H1N1 infection and were summarized in this systematic review. A literature review. Ann Fr Anesth Reanim , Crit Care Med , J Extra Corpor Technol , PubMed Google Scholar.

JAMA , BMJ , b Stang A: Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol , Article PubMed Google Scholar. Crit Care , R Eur J Emerg Med , PLoS One , 5: e Intensive Care Med , Anaesth Intensive Care , Minerva Anestesiol , Gatherer D: The H1N1 influenza outbreak in its historical context. J Clin Virol , Curr Opin Crit Care , Crit Care Med , e Extracorporeal Life Support Organization, Version April Interact Cardiovasc Thorac Surg , Contemp Clin Trials , Download references.

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