BMJ  2005;330:1475 (25 June), doi:10.1136/bmj.330.7506.1475

Paper

The role of healthcare delivery in the outcome of meningococcal disease in children: case-control study of fatal and non-fatal cases

¹ Infectious Diseases Unit, Department of Paediatrics, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London W2 1PG, ² Research Unit, Royal College of Paediatrics and Child Health, London W1W 6DE, ³ Faculty of Health and Social Care, University of the West of England, Bristol BS16 1DD, ⁴ Paediatric Intensive Care Unit and Paediatric Accident and Emergency Department, St Mary's Hospital, London W2 1PG, ⁵ Department of Paediatrics, Kingston Hospital, Kingston upon Thames KT2 7QB, ⁶ Centre for Child Health, Queen Mary's School of Medicine and Dentistry, University of London, London E1 1BB

Abstract

Objective To determine whether suboptimal management in hospital could contribute to poor outcome in children admitted with meningococcal disease.

Design Case-control study of childhood deaths from meningococcal disease, comparing hospital care in fatal and non-fatal cases.

Setting National statistics and hospital records.

Subjects All children under 17 years who died from meningococcal disease (cases) matched by age with three survivors (controls) from the same region of the country.

Main outcome measures Predefined criteria defined optimal management. A panel of paediatricians blinded to the outcome assessed case records using a standardised form and scored patients for suboptimal management.

Results We identified 143 cases and 355 controls. Departures from optimal (per protocol) management occurred more frequently in the fatal cases than in the survivors. Multivariate analysis identified three factors independently associated with an increased risk of death: failure to be looked after by a paediatrician, failure of sufficient supervision of junior staff, and failure of staff to administer adequate inotropes. Failure to recognise complications of the disease was a significant risk factor for death, although not independently of absence of paediatric care (P = 0.002). The odds ratio for death was 8.7 (95% confidence interval 2.3 to 33) with two failures, increasing with multiple failures.

Conclusions Suboptimal healthcare delivery significantly reduces the likelihood of survival in children with meningococcal disease. Improved training of medical and nursing staff, adherence to published protocols, and increased supervision by consultants may improve the outcome for these children and also those with other life threatening illnesses.

Introduction

Although treatment of meningococcal disease on a paediatric intensive care unit improves outcome,^{1 2} most patients present to their nearest emergency department and many deteriorate so rapidly that death from shock and multiorgan failure often occurs before transfer to a specialist paediatric intensive care unit. The speed with which the diagnosis is made, antibiotics administered, and the complications of shock and multiorgan failure treated is likely to be a major determinant of outcome.³ To test the hypothesis that outcome depends on the quality of health care early in the disease we undertook a national, blinded, case-control study of healthcare delivery in the first 24 hours after admission to hospital in children who died from meningococcal disease compared with those who survived.

Methods

We identified cases of meningococcal disease in children aged 0-16 years between 1 December 1997 and 28 February 1999. For each death (case) we identified three survivors (controls) from the same region of the country matched for age, corresponding to different risks of mortality.⁴

A major problem in both the design and analysis of this study was how to control for the expected differences in severity of disease between fatal and non-fatal cases. The children who died were probably more ill than those who survived and would therefore require more medical interventions, which in itself could give rise to greater opportunity for treatment failure. At presentation to hospital, however, children who eventually die are not always sicker than those who survive (see bmj.com). To study failures of healthcare delivery we identified children who initially presented with mild disease or severe illness and then controlled for the differences in severity of disease in multivariate analysis. To obtain a large enough group of survivors who were severely ill we recruited three controls for each case.

To control for disease severity we used the Glasgow meningococcal septicaemia prognostic score, which has been shown to predict outcome.⁵ We also controlled for known factors such as disease presentation (septicaemia or meningitis) and meningococcal serogroup. We included the presence of organ failure as a covariate in the multivariate analysis because it is a reliable indicator of disease severity. Finally we assessed failings of fluids and inotrope management in a subgroup of patients who developed cardiovascular failure. See bmj.com for details. Copies of the complete hospital medical and nursing records were received.

Standardised evaluation of emergency medical care
Development of a standardised assessment tool
To provide an objective assessment of the promptness and quality of emergency medical care provided, we developed a standardised assessment tool using published and widely accepted criteria for diagnosis and management of meningococcal disease and its complications.⁶ We defined the following disease complications (organ failures) namely: cardiovascular failure (shock), respiratory failure, neurological failure, raised intracranial pressure, and haemorrhagic rash.

Panel
An assessment panel—comprising a consultant in paediatric emergency medicine, a consultant in paediatric infectious diseases, and two consultants in paediatric intensive care—reviewed data on all cases.

Blinded evaluation of patient records using the standardised assessment tool
Vital signs and laboratory results recorded in each patient's notes in the first 24 hours after admission were transcribed on to flow charts in one hour time periods with the time of arrival at hospital taken as time 0 hours. The treatments initiated were also recorded for each hour. The clinical findings and laboratory results were then presented to the panel by revealing the information available at each hour after admission. On the basis of the information available at each hour, the panel members assessed each patient for the presence of diagnostic features of meningococcal disease and its complications. Using the agreed protocol⁷ they recommended standard management of each complication. The panel members became aware of the outcome (fatal or not) only after their scoring had been recorded.

We evaluated the actual hospital management, both in terms of timing and the actions undertaken. Delay of more than an hour between the action recommended by the panel and what actually occurred was defined as a failure of care and delay of more than 24 hours in being seen by a consultant as a failure in supervision. The panel assessed whether the failure in care resulted from a failure to recognise the complication or a failure to recognise the severity and to adhere to the protocol. The panel scored all patients on admission with the Glasgow meningococcal septicaemia prognostic score,⁵ and patients were assigned to three groups based on objective clinical features: meningitis, septicaemia, or a mixed picture. We also recorded what sort of team (paediatric or adult) primarily cared for the child.

Statistical methods
We used multivariate conditional logistic regression on matched data with death/survivor status as the outcome variable and failures of care as explanatory variables. We evaluated a "full" model, which included all the failures of care as well as the effects of potential confounders. We then used the likelihood ratio test to compare this full model with nested models comprising a subset of failure variables.

Results

During the study period 190 deaths and 755 survivors were notified of which 143 cases and 355 controls were included in the study. Organ failure was present in 141 children who died and 169 survivors.

Univariate analysis
Failures in management were significantly more common in children who died than in survivors. With the exception of serogroup, probability of death was significantly correlated with Glasgow meningococcal septicaemia prognosis score, presence of organ failure, and disease type. Failure to recognise complications, failure to appreciate disease severity, failure in supervision, lack of involvement of a paediatric team in care, and inadequacies of fluid and inotrope administration were all significantly associated with death. Multiple treatment failures significantly increased the risk of death (see bmj.com).

Multivariate analysis
The full model indicates that not being under the care of a paediatrician, failure of supervision, and failure to administer inotropes are independent risk factors for death (table 1). Not being under paediatric care was highly correlated with a failure to recognise complications (P = 0.002; Fisher's exact test). When we removed absence of paediatric care from the model, failure to recognise disease complications became highly significant (6.1, 1.7 to 22; P = 0.006, table 1). This association suggests that failure to recognise complications is one of the consequences of absence of paediatric care. Using the risk factors identified in the multivariate analysis, we found the odds ratio for death with one failure increased with additional failures (table 2).

View this table: [in this window] [in a new window]   Table 1 Multivariate model of treatment of children with meningococcal disease who died or survived (R2=79%). Odds ratios (OR) are for death

 

View this table: [in this window] [in a new window]   Table 2 Multivariate model for multiple failures, with odds ratios for death in children presenting with meningococcal disease

 

Discussion

We found a highly significant increase in the frequency of departures from optimal care in children who died compared with those who survived. Significant independent risk factors for death included not being treated by a paediatric team, not being supervised by a consultant, and inadequate inotrope therapy. Our multivariate analysis also suggests that failure to recognise complications was a significant risk factor for death, although not independently of absence of treatment by a paediatric team. Given that these two failures are highly correlated we suggest that failure to recognise complications is one of the consequences of absence of paediatric care.

The criteria used by the panel to diagnose the complications of meningococcal disease were based on widely accepted and published criteria, which depend on clinical observation easily determined by any medical and nursing team. They also use simple biochemical (blood gases) or monitoring (pulse oximetry) technologies, which are readily available in all district hospitals. All treatments recommended by the panel were based on published protocols of management.^{7 8 9} The panel used objective findings recorded in the clinical notes to assess the disease and its complications. It therefore seems that when the panel decided failures had occurred, these resulted from a medical team either not appreciating the importance of clear physical signs or laboratory results or not following published management protocol.

Why care may be suboptimal
Vital signs were often inadequately documented in the nursing records. If signs of compensated shock were recorded but not appreciated, delays in diagnosis and treatment were inevitable. Many children with signs of shock were not recognised as seriously ill. Often this seemed to be due to their care being undertaken mainly by doctors trained to recognise serious illness in adults.

We found that children being looked after by doctors without paediatric training were at increased risk of dying. Lack of supervision by a consultant was also an independent risk factor for death. The significantly increased odds ratio for death associated with failure to administer appropriate inotrope therapy emphasises the importance of protocols for management of meningococcal disease.

Conclusions
Earlier recognition of the signs and symptoms of meningococcal infection may lead to earlier diagnosis, earlier treatment intervention, and reduced risk of a fatal outcome. Meningococcal disease shares many features with other life threatening acute illnesses. The difficulties in recognition of the seriously ill child and in treatment of shock and organ failure that we have examined in the context of meningococcal disease might be equally apparent in the management of children with other life threatening disorders.

What is already known on this topic Overall mortality from meningococcal disease has not changed significantly in the past few decades, though recent studies have shown improved outcomes in children treated aggressively in paediatric intensive care units Meningococcal disease can progress very rapidly Most children with meningococcal sepsis present to their local hospital and many die before they can be transferred to specialist intensive care units What this study adds The quality of healthcare delivery in hospital for children with meningococcal disease differs in fatal and non-fatal cases Optimal early management of septicaemia and meningitis at the admitting hospital can improve outcome Improved outcome is associated with children being managed by paediatric teams and junior doctors being supervised by consultants Doctors should follow published protocols of care for fluid resuscitation, inotrope therapy, and referral to paediatric intensive care units

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This is the abridged version; the full version is on bmj.com

We dedicate this paper to the late Professor David Baum. We thank Roddy McFaul for his help; all local hospital staff and regional paediatric intensive care; public health staff at CDSC including Mary Ramsay, Norman Begg, and James Stuart; Ed Kaczmarski of the Meningococcal Reference unit in Manchester; the district consultants in communicable disease control; and the regional epidemiologists. We are grateful to all the parents who participated, especially those recently bereaved.

Contributors: See bmj.com

Funding: This study was supported by a grant from the Meningitis Research Foundation.

Conflict of interests: None declared.

Ethical approval: South Thames multi-research ethics committee and all local research ethics committees in England, Wales, and Northern Ireland approved the study.

References

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2. Thorburn K, Baines P, Thomson A, Hart CA. Mortality in severe meningococcal disease. Arch Dis Child 2001;85: 382 -5.[Abstract/Free Full Text]
3. Nadel S, Britto J, Booy R, Maconochie I, Habibi P, Levin M. Avoidable deficiencies in the delivery of healthcare to children with meningococcal disease. J Accid Emerg Med 1998;15: 298 -303.[Abstract/Free Full Text]
4. Stuart JM, Monk PN, Lewis DA, Constantine C, Kaczmarski EB, Cartwright KAV. Management of clusters of meningococcal disease. Commun Dis Rep CDR Rev 1997;7: R3 -5.[Medline]
5. Thomson APJ, Sills JA, Hart CA. Validation of the Glasgow meningococcal septicaemia prognostic score: a 10 year retrospective survey. Crit Care Med 1991;19: 26 -30.[Web of Science][Medline]
6. Nadel S, Levin M, Habibi P. Treatment of meningococcal disease in childhood. In: Cartwright K, ed. Meningococcal disease. New York: John Wiley, 1995: 207 -43.
7. Pollard AJ, Britto J, Nadel S, DeMunter C, Habibi P, Levin M. Emergency management of meningococcal disease. Arch Dis Child 1999;80: 290 -6.[Free Full Text]
8. Pathan N, Nadel S, Levin M. Pathophysiology and management of meningococcal septicaemia. J R Coll Physicians London 2000;34: 436 -44.[Medline]
9. Advanced Life Support Group. Advanced paediatric life support manual. London: BMJ Publishing Group, 2001.

(Accepted 20 April 2005)

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