Therapeutic challenges and treatment of hypovolaemic shock in severe malnutrition

Summary of proceedings¹

A severely malnourished child attending the Kilifi programme

A recent article by Maitland on therapeutic challenges in the treatment of severe malnutrition focuses on the identification of children with sepsis and on fluid management strategies.

The World Health Organisation (WHO) has developed consensus management guidelines for the treatment of severe malnutrition. These include a stabilisation phase during which life threatening problems are identified and treated, a staged introduction of milk-based nutritional rehabilitation, micronutrient and vitamin supplementation and empirical use of antimicrobial and aniti-helminth treatments. It is argued that with strict adherence to these guidelines, the mortality should be <5%. Whilst high case-fatality rates are often attributed to faulty case management, the evidence for this assertion is poor. Other workers have suggested that outcome is largely dependent on other factors, including the frequency of additional life-threatening complications.

At Kilifi District Hospital on the coast of Kenya, severe malnutrition is a common cause of admission. Here, 400-500 paediatric cases are treated annually. The current management approaches the gold standard recommended by the WHO. However, in-hospital mortality remains at approximately 20% and has been stable over time, despite in-service training and expansion of the dedicated nutrition team. In Kalifi hospital, the largest group of cases comprises children with uncomplicated malnutrition. For these children, the management and in-patient survival approaches the standard recommended by the WHO guidelines. However, a substantial group of children present with severe illness and life threatening complications and represent a major challenge to successful management.

A prospective study of children with severe malnutrition at Kilifi hospital has been conducted over the last decade which has identified a number of areas of concern in relation to management. Early mortality is of particular concern, as > 40% of deaths have been found to occur within 72 hours of admission. This finding suggests that triage, early identification and adequate treatment of life threatening complications are inadequate and need more careful scrutiny. In 2005, the Kilifi Severe Malnutrition Research Programme was established in order to systematically evaluate the current WHO management guidelines.

Gastroenteritis and dehydrating diarrhoea

Diarrhoea and dehydration at Kilifi District Hospital are managed in accordance with WHO policy. The results of the 2-year prospective study (June 2005-May 2007) include 667 children with severe malnutrition (10% of all hospital admissions). A total of 325 children (49%) were admitted with a history of diarrhoea, of which seventy-seven (24%) died. This compares unfavourably with 14% of the 342 cases that died which were uncomplicated by diarrhoea. Of note is the poor performance of the WHO danger signs (advanced shock defined as impaired consciousness together with capillary refill > 3s, a weak pulse volume and a temperature gradient) to identify those children at risk of dying and the limited number that would qualify for intravenous rehydration. Despite severe biochemical derangement and other features of shock, only one of the 325 children with a history of diarrhoea was found to be eligible for intravenous fluid rehydration at admission. Fatal cases were more frequently found to be complicated by clinical evidence of dehydration or impaired perfusion, severe acidosis or electrolyte imbalance and invasive bacterial infection. A further ninety-eight children were found to develop diarrhoea after admission, of which 21% died. It was noted that in both groups, a number of children developed profuse osmotic diarrhoea. The author concluded that under the current WHO guidelines, intravenous fluid resuscitation is reserved for too few cases with signs of advanced shock, when it is probably too late. Thus fluid resuscitation is often associated with high mortality.

The use of the standard WHO oral rehydration solution (ORS) with 90 mmol Na/l for severely malnourished children (ReSoMal) has been cautioned because of its relatively high concentration of Na and low concentration of K. WHO has changed the formulation for ORS for non-malnourished children. Given the safety concerns surrounding ReSoMal, the introduction of a new standard ORS with lower Na content and higher K, and the author's observations that mortality remains high on current management, the author argues that prospective evaluation is warranted to compare ReSoMal against the new standard WHO ORS.

Treatment of hypovolaemic shock: phase 1 and 11 clinical trials

Current WHO guidelines recommend that children with severe malnutrition should not routinely receive intravenous fluids. Fluid resuscitation should be reserved for those with signs of decompensated shock. In this situation, treatment guidelines recommend an initial bolus of halfstrength Ringers lactate, half-strength Darrow's solution or 0.45% (w/v) saline followed by wholeblood transfusion if the child fails to improve. The author of the study argues that these recommendations are based on two largely unproven concerns around salt and water overload and incipient heart failure. Limitations in these guidelines are highlighted. These include the fact that hypotonic fluids represent a much greater risk of fluid overload and that the use of blood as a volume expander is physiologically unsound.

The author cites two trials which have been conducted to examine volume expansion in severely malnourished children with shock secondary to diarrhoea or severe sepsis.

In the first phase, a single-arm prospective study examined the safety and efficacy of the current WHO shock treatment protocol in up to twenty children with severe malnutrition. In the second phase, a randomised control trial was conducted to examine the safety and efficacy of different intravenous replacement regimens compared with the standard WHO protocol. The intervention arms were full-strength Ringers lactate in the group with diarrhoea and a three arm trial (WHO treatment vs 5% albumin vs fullfullstrength Ringers lactate) in the group with septic shock. In the first phase, recruitment was terminated after six of the seven children enrolled died. Most deaths were a result of uncorrected shock. In the second phase, trial mortality was high (54%). There was a non-significant trend towards a higher mortality in the WHO arm compared with the Ringers lactate arm. In all arms (WHO, Ringers lactate and albumin) the safety of the intervention fluids was demonstrated. It was concluded that fluid resuscitation with an isotonic solution should be re-evaluated prospectively in dose-escalation studies or by end-point directed treatment.

Myocardial function and response to treatment

In severe malnutrition there are limited data on cardiac function in children, with conflicting conclusions. A study in Jamaica concluded on the basis of reduced cardiac output that there was marked impairment of cardiac function. A study on Zairian children indicated that many children have signs of an adaptive hypo-circulatory state and some show frank peripheral circulatory failure comparable with hypovolaemic shock. Neither of these studies examined the response to volume expansion or other therapies.

Echo-cardiographic examinations and Doppler assessment of cardiac output using an ultrasound cardiac monitor have been undertaken. Initial examinations were conducted in children with clinical features of shock just before or after fluid resuscitation stabilisation of the child. Evidence of cardiac failure is not supported by the findings. Markedly reduced cardiac output concurrent with increased systemic vascular resistance was observed. Taken together with the finding of the fluid trial these results point to substantial volume depletion and reduced cardiac output.

What is apparent is that there are many lessons to be learnt across the specialities, from Africa to UK and vice versa. The clinical experience of managing severe malnutrition in Africa is complicated by severe electrolyte perturbations, shock and complex complications of gastroenteritis. These have also been highlighted in the management of difficult, complex gastro-enterological and nutritional problems and the refeeding syndrome.

Maitland concludes that resolving some of the complex and unresolved clinical therapeutic issues of African children with severe malnutrition requires a multi-disciplinary approach that may benefit from including international experts in nutrition, gastroenterology paediatric sepsis and critical care. This approach could be the basis on which to develop a programme of severe malnutrition research to address the fundamental scientific and treatment gaps that result in high in-hospital mortality in children with severe malnutrition in Africa. Valuable lessons may be learned by sharing experiences with specialists managing complex nutritional problems on both sides of the equator.

¹Maitland. K (2009). Symposium 5: Joint BAPEN and Nutrition Society Symposium on 'Feeding size 0: the science of starvation'. Severe Malnutrition: therapeutic challenges and treatment of hypovolaemic shock. Proceedings of the Nutrition Society (2009), vol 68, pp 274-280