SCCM Resource Library-Multiple Organ Dysfunction and PELOD-2 Score in Pediatric Cerebral Malaria

Video Transcription

Hi, my name is Hunter Johnson and I am a Pediatric Critical Care Medicine Fellow at Nationwide Children's Hospital in Columbus, Ohio.  Today, I want to share about my research in multiple organ dysfunction syndrome and the PILAD2 score in pediatric cerebral malaria, and I have no disclosures.  Every year, malaria results in more than 400,000 deaths worldwide, with 94% of all malaria cases and deaths occurring in Africa, mostly in children less than 5 years of age.  Cerebral malaria, which is defined as Blantyre Coma Score less than or equal to 2, Plasmodium  falciparum parasitemia, and no other discernible cause of coma, is one of the most severe manifestations of malaria.  Despite advances in both malaria prevention and treatment, mortality rates in children with cerebral malaria continue to range from 15 to 40%, with neurological sequelae identified  in up to 50% of survivors. As a result of its unique ability to adhere to endothelium, Plasmodium falciparum can be found in the microvasculature of many organs within its host.  Based on the current literature, an estimated 33 to 85% of adult patients with Plasmodium falciparum malaria have MODS when using the Sequential Organ Failure Assessment, or the  SOFA score, to define organ dysfunction. While MODS is reported as a frequent complication of severe malaria in adults, it has not been well described in children.  MODS in this population is clinically significant because of the increased mortality rates reported  in adult malaria patients with MODS, which is as high as 48% compared to those with less than two organ systems involved, which is closer to 6%.  And then there are similar differences in mortality rates in adults when comparing those with cerebral malaria and those with cerebral malaria and multi-organ dysfunction syndrome.  Autopsy studies have demonstrated significant sequestration of parasites within the brain, heart, lungs, spleen, stomach, intestines, and skin in children with cerebral malaria.  So therefore, it's plausible that multiple organ dysfunction syndrome is also present in pediatric patients with cerebral malaria, but our current understanding of MODS in this  patient population is lacking. We hypothesize that when applying a quantitative scoring system, the PILAD2 score, that children  with cerebral malaria would have evidence of multi-organ dysfunction, and also that higher PILAD2 scores on admission would be associated with increased mortality.  This was a retrospective study of prospectively gathered data from January 2019 to June 2021 at Queen Elizabeth Central Hospital in Blantyre, Malawi.  Data required for the calculation of each of the five sub-scores that comprise the PILAD2 score were extracted for each patient, and then criteria were met for organ dysfunction  if the score was greater than zero in any organ-specific sub-score. If more than one organ system had a score greater than zero, the patient was diagnosed  with MODS and the total PILAD2 score was calculated and recorded. There were a few modifications made, so for example, the neurologic sub-score, the Blantyre  coma score, was used instead of the Glasgow coma score since the BCS was recorded on admission for each patient and is much more commonly used in children with cerebral malaria.  Additionally, the SpO2 to FiO2 ratio, or the SF ratio, was used instead of the PaO2 to FiO2  ratio since arterial blood gases are not routinely obtained as part of the standard of care.  We then performed an ROC curve analysis to determine the capacity of the PILAD2 score on admission to predict mortality, and then differences between the PILAD2 scores of survivors  and non-survivors were analyzed using the Fisher's exact test.  There were 145 patients admitted between January 2019 and June 2021 whose charts were reviewed.  135 patients, or 93%, met criteria for multiple organ dysfunction syndrome based on their PILAD2  scores. 10 patients, or 7%, had only neurologic dysfunction at the time of admission,  and then additional organ system involvement, as you can see in this table here,  included hematologic, which was in 77% of our patients, renal in 61%, cardiovascular in 44%,  and then respiratory in 1 patient. The median PILAD2 score on admission was 4 in our survivors  and 6.5 in the non-survivors. This had a p-value of less than 0.0001. When the neuro-subscore was  removed, it's interesting to note that the total PILAD2 score remained higher in the non-survivors.  36 patients, or 25%, had 2 organs involved. 68 patients, or 47%, had dysfunction of 3 organs,  and then the remaining 31 patients, or 21%, had 4 organs affected. There was no significant  difference between the number of organ systems involved in our survivors versus our non-survivors.  And then the different combinations of organs involved are illustrated in this table here. In our survivors versus our non-survivors. And then the different combinations of organs  involved are illustrated in the figure on the left. Overall mortality for the cohort was 15%,  with an N of 22. The median PILAD2 score on admission was 4 in those who survived, and 6.5 in those who did not survive the discharge. And that is illustrated here  in this ROC analysis, which showed that admission PILAD2 score predicted mortality with an AUC of 0.75. The optimum cut point was a PILAD2 score of greater than 5.5,  and then the sensitivity and specificity for this cut point are 68% and 74%, respectively.  So why is this important? Well, malaria continues to result in significant morbidity and mortality  across the world. Despite autopsy studies showing evidence of multi-organ sequestration of the parasites in pediatric patients with cerebral malaria, there's only one small study  of 17 patients showing the incidence and effect of MODS on mortality. So due to the lack of evidence  on this question, we applied a scoring system that's widely used and accepted in critically ill pediatric patients to identify MODS and evaluate the effect of this complication on  mortality. In our large cohort using a PILAD2 score, we found evidence of MODS in 93% of our patients at the time of admission. Neurologic dysfunction was present by definition.  The hematologic system was the second most affected organ system, which is not surprising  since thrombocytopenia is a well-recognized common complication of malaria. The renal system was the  third most affected organ system, and then almost half of our cohort had cardiovascular  dysfunction as well. The presence of MODS was associated with increased mortality in our cohort  of patients, and additionally, non-survivors were found to have higher PILAD2 scores at the time  of admission. There is no significant difference in the number of organ systems affected, which  suggests that the association with outcome may be related more to the severity of the involvement  of the affected organs. The increase in mortality in pediatric cerebral malaria patients in the  presence of MODS illustrates the need for improved awareness of MODS, so that way management strategies for these patients can include appropriate multi-organ, multi-system support.  So what does this look like practically? Well, if a child with cerebral malaria has cardiovascular  dysfunction, maintaining appropriate cerebral perfusion pressure without pharmacologic assistance,  especially if intracranial hypertension is present, can be quite difficult. A cerebral  malaria patient with renal dysfunction may be at risk for worsening neurologic dysfunction due to  uremic encephalopathy, or they may have severe electrolyte derangements that need to be addressed.  I would also like to note that multiple combinations of organ dysfunction were observed in this large cohort, and further work is needed to evaluate the effects of each combination  on overall morbidity and mortality. So our work has several limitations. It's a retrospective  study that took place in a resource-limited setting. Therefore, missing data occurred when  testing strips or laboratory reagents were not available, and in these cases, we scored the  missing data as normal, and this could have resulted in underestimating the overall frequency,  as well as severity of MODS in multiple patients. We may have underestimated the presence of renal  failure, for example. In this cohort, since 15 patients, or 10 percent, were missing a creatinine  at the time of admission. And then the potential limitations of the PILOD2 scoring system itself  should be considered when used in this population. So for example, for the respiratory system, the  PILOD2 score includes points for being ventilated, and this is not a common intervention where malaria  is endemic. In conclusion, multiple organ dysfunction syndrome is prevalent in pediatric  patients with cerebral malaria. MODS is associated with increased mortality in this population, and admission PILOD2 scores may objectively identify children with cerebral malaria  at highest risk of mortality, allowing for the allocation of limited resources. Given the frequency of MODS that we identified, recognizing additional organ systems involved is  essential when providing patient care and making management decisions in order to provide the  appropriate adjunctive therapies that are needed. Future work is needed to create a new validated  scoring system for this patient population, as well as apply this new scoring system to patients with other types of severe malaria. Thank you so much for your time.

Video Summary

Hunter Johnson, a Pediatric Critical Care Medicine Fellow, discusses his research on multiple organ dysfunction syndrome (MODS) in pediatric cerebral malaria. He conducted a retrospective study using the PILAD2 score to assess organ dysfunction and its association with mortality in patients. Out of 145 patients, 93% exhibited MODS, with cardiovascular dysfunction being the most common, followed by renal dysfunction. The presence of MODS was associated with increased mortality, and higher PILAD2 scores on admission were correlated with higher mortality rates. Johnson emphasizes the need for improved awareness of MODS in cerebral malaria to provide appropriate multi-organ support. Further research is required to evaluate specific organ dysfunction combinations and their impact on morbidity and mortality.

Asset Subtitle

Infection, Sepsis, Pediatrics, 2022

Asset Caption

INTRODUCTION/HYPOTHESIS: Globally, malaria results in 409,000 deaths annually, the majority of which occur in children less than five years of age. Cerebral malaria (CM) is the most severe manifestation of the disease with case fatality rates of up to 40%. Autopsy results in children with CM have demonstrated sequestration of Plasmodium falciparum parasites not only within the brain, but also in the heart, lungs, spleen, stomach, intestines, and skin. Thus, it is plausible that multiple organ dysfunction syndrome (MODS) is present in pediatric patients with CM, but the frequency of MODS and its association with mortality in this patient population has not been well described. METHODS: This is a retrospective review of prospectively gathered data in children 6 months to 12 years of age admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi between January 2019 and June 2021. All patients met the World Health Organization case definition for CM. Physical exam findings and laboratory values necessary to calculate a Pediatric Organ Logistic Dysfunction-2 (PELOD-2) score were abstracted. RESULTS: A total of 138 patients were included with a mean age of 59 months. Overall mortality for the cohort was 15% (n=20). Only 7 patients (5%) had single organ dysfunction, while 34 (25%) had two organs involved, 66 (48%) had dysfunction of three organs, and the remaining 31 (22%) patients had four organs affected. In addition to neurologic dysfunction, other organ systems involved included hematologic (80%), renal (62%), cardiovascular (45%), and respiratory (1%). The mean PELOD-2 score on admission was 4.7 (±2.3) in those who survived to discharge and 7.4 (±3.2) in the patients who died (p < 0.0001). An ROC analysis showed that admission PELOD-2 score predicted mortality with an AUC of 0.77. CONCLUSIONS: Multiple organ dysfunction is nearly ubiquitous in pediatric patients with cerebral malaria. PELOD-2 score at the time of hospital admission may objectively identify children with CM at highest risk of mortality allowing for the allocation of limited resources.

Meta Tag

Content Type Presentation

Knowledge Area Infection

Knowledge Area Sepsis

Knowledge Area Pediatrics

Knowledge Level Advanced

Membership Level Select

Tag Infectious Diseases

Tag Multiple Organ Dysfunction

Tag Pediatrics

Tag Tropical Medicine

Year 2022

Keywords

Pediatric Critical Care Medicine Fellow

multiple organ dysfunction syndrome

pediatric cerebral malaria

retrospective study

PILAD2 score

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