Children with malignancies and septic shock - an attempt to understand the risk factors

Abstract Objectives: To explain the high mortality of septic shock in children with cancer. Methods: A retrospective cohort from 2016 to 2020, of children aged 0 to 18 years, and septic shock. Results: The authors included 139 patients. Acute lymphocytic leukemia was the most frequent diagnosis (16.5%), and Gram-negative bacteria were the most frequent blood culture isolates (22.3%). There were 57 deaths in ICU (41%), 10 in the first 24 hours of shock (early death). A LASSO model with variables: neutropenia (coefficient 0.215), respiratory (0.81), hematological (1.41), and neurological (0.72) dysfunctions, age (-0.002) and solid tumor recurrence (0.34) generated AUC = 0.79 for the early death outcome. Survivors had significant differences in the PRISM-IV score (mean ± SD 10.9 ± 6.2 in the survivors, 14.1 ± 6.5 in the deceased, p = 0.004), and in the mean number of organ dysfunctions (3.2 ± 1.1 in the survivors, 3.8 ± 6.5 in the deceased, p < 0.001). A positive fluid balance in the first 24 hours of sepsis between 2% and 6% of body weight showed a reduction effect on the probability of death in ICU (hazard ratio 0.47, 95% CI 0.24-0.92, p = 0.027). The recurrence of any cancer was a predictor of in-hospital death, regardless of severity. Conclusions: Recurrence of any cancer is an important risk of sepsis-related death. A positive fluid balance between 20 and 60 mL/kg or 2% and 6% of body weight in the first 24 hours after the onset of sepsis is related to lower mortality.

Children with malignancies and septic shock - an attempt to understand the risk factors.

OBJECTIVES: To explain the high mortality of septic shock in children with cancer. METHODS: A retrospective cohort from 2016 to 2020, of children aged 0 to 18 years, and septic shock. RESULTS: The authors included 139 patients. Acute lymphocytic leukemia was the most frequent diagnosis (16.5%), and Gram-negative bacteria were the most frequent blood culture isolates (22.3%). There were 57 deaths in ICU (41%), 10 in the first 24 hours of shock (early death). A LASSO model with variables: neutropenia (coefficient 0.215), respiratory (0.81), hematological (1.41), and neurological (0.72) dysfunctions, age (-0.002) and solid tumor recurrence (0.34) generated AUC = 0.79 for the early death outcome. Survivors had significant differences in the PRISM-IV score (mean ± SD 10.9 ± 6.2 in the survivors, 14.1 ± 6.5 in the deceased, p = 0.004), and in the mean number of organ dysfunctions (3.2 ± 1.1 in the survivors, 3.8 ± 6.5 in the deceased, p < 0.001). A positive fluid balance in the first 24 hours of sepsis between 2% and 6% of body weight showed a reduction effect on the probability of death in ICU (hazard ratio 0.47, 95% CI 0.24-0.92, p = 0.027). The recurrence of any cancer was a predictor of in-hospital death, regardless of severity. CONCLUSIONS: Recurrence of any cancer is an important risk of sepsis-related death. A positive fluid balance between 20 and 60 mL/kg or 2% and 6% of body weight in the first 24 hours after the onset of sepsis is related to lower mortality.

PRISM 4-C: An Adapted PRISM IV Algorithm for Children With Cancer.

We evaluated the performance of PRISM IV for pediatric cancer patients, and adapted and calibrated the algorithm to calculate mortality probabilities for these patients. An ambidirectional cohort was used, and data were collected from March 2017 prospectively to April 2019, and retrospectively to November 2014. The derivation set for model building contained 500 patients, and a validation set of 503 patients. Risk variables for hospital death were tested in logistic regression models encompassing PRISM IV components. There were 128 deaths (12.7%), being 65 deaths in the validation set. In the validation set, the PRISM IV algorithm had an area under the receiver operating characteristic curve of 0.89, with P=0.13 by Hosmer-Lemeshow test, and predicted 33 of the 65 deaths for a standardized mortality rate of 1.8 (95% confidence interval, 1.4-2.9; P<0.001 by Mid-P test). Our modified algorithm had an area under the receiver operating characteristic curve of 0.93, with P=0.3 by Hosmer-Lemeshow test and an standardized mortality rate of 1.02 (95% confidence interval, 0.79-1.19). The modified algorithm predicted 63.7 of 65 deaths. The PRISM IV algorithm was a poor predictor of mortality in children with cancer. The modified algorithm improved the predictive performance.

Vancomycin Therapeutic Targets and Nephrotoxicity in Critically Ill Children With Cancer.

To obtain pharmacokinetic and pharmacodynamic data for vancomycin in a cohort of critically ill pediatric oncology patients, we analyzed 256 measurements of vancomycin concentrations in 94 patients. Variables were tested as possible risk factors for vancomycin-related nephrotoxicity or death for 28 days. We found the following: mean vancomycin trough serum concentration, 15.6 ± 12.4 µg/mL; mean vancomycin clearance, 0.16 ± 0.098 L/h/kg; and mean vancomycin distribution volume, 1.04 ± 0.11 L/kg. Only 13.6% of serum trough level measurements were between 15 and 20 µg/mL. The trough levels showed a strong correlation with the AUC (area under the curve of serum concentrations vs. time over 24 h to the minimum inhibitory concentration ratio), with a 94% positive predictive value for AUC/MIC ≥ 400, but only for MIC=1. The doses that are currently used (60 mg/kg/d) attained the therapeutic target (AUC/MIC ≥ 400) in only 56% of measurements, considering MIC=1. A serum trough level of ≥ 20 µg/mL was an independent risk for nephrotoxicity (P = 0.0008; odds ratio = 17.83). Vancomycin-related nephrotoxicity was a predictor of death for up to 28 days (P = 0.003, odds ratio = 7.68). Currently administered doses of vancomycin do not reach the therapeutic target for critical cancer patients, particularly if staphylococci isolates have a MIC>1.

Agreement and correlation of pH, bicarbonate, base excess and lactate measurements in venous and arterial blood of premature and term infants

BACKGROUND AND OBJECTIVES: Determine the extent of agreement and correlation between arterial samples and venous (obtained from a venous umbilical catheter), with respect to measurements of pH, bicarbonate, base excess and lactate, in critically ill term and premature newborns. METHODS: Arterial blood samples (0.5-1 mL) were obtained for gas analysis by radial artery puncture, and, within the limit of 5 minutes, samples were obtained from venous umbilical catheters. Bland-Altman plots were used to depict agreement between arterial and venous measurements. Limits of agreement were defined as the mean difference ± 2SD (Standard Deviation). Correlation was assessed by Pearson's method. RESULTS: A hundred and six samples (53 pairs) were taken from 53 patients for analysis of bicarbonate, pH and base excess. Lactate was analyzed in 49 pairs of samples. Differences were within the limits of agreement in 94.3 percent of pairs of samples for pH, and the same percentage was observed for bicarbonate. There was agreement in 96.2 percent of pairs for base excess, and in 91.8 percent for lactate. Mean differences were 0.03 units for pH, -1.2 mmol/L for bicarbonate, -0.24 mmol/L for base excess and 0.33 mmol/L for lactate. Pearson's correlation coefficients (r) were 0.87 for pH, 0.76 for bicarbonate, 0.86 for base excess and 0.95 for lactate. CONCLUSIONS: Although single venous values cannot be used as equivalent to arterial for assessing acid base status in newborns, venous blood samples can be used serially for monitoring trends over time.

JUSTIFICATIVA E OBJETIVOS: Determinar o grau de concordância e correlação entre amostras arteriais e as obtidas através de um cateter venoso umbilical, com relação ao pH, bicarbonato, excesso de base (BE) e lactato, em recém-nascidos prematuros e de termo, criticamente doentes. MÉTODO: Foram obtidas amostras para gasometria (0,5 - 1 mL), por punção de artéria radial, e, dentro do limite de 5 minutos, do cateter venoso umbilical. O método de Bland-Altman foi utilizado para demonstrar a concordância entre as medidas. Os limites de concordância foram definidos como a diferença média ± 2 DP. Para as correlações foi utilizado o método de Pearson. RESULTADOS: Cento e seis amostras (53 pares) de 53 pacientes foram analisadas para bicarbonato, pH e BE. Foi dosado lactato em 49 pares de amostras. Houve concordância em 94,3 por cento dos pares de amostras para o pH, e este mesmo percentual foi observado para o bicarbonato. Para o excesso de base, a concordância foi de 96,2 por cento, e de 91,8 por cento para o lactato. As diferenças médias foram 0,03 unidade para o pH, -1,2 mmol/L para o bicarbonato, -0,24 mmol/L para o excesso de base e 0,33 mmol/L para o lactato. Os coeficientes de correlação de Pearson (r) foram 0,87 para o pH, 0,76 para o bicarbonato, 0,86 para o excesso de base e 0,95 para o lactato. CONCLUSÕES: Os valores venosos isolados não podem ser usados como equivalentes aos arteriais para a avaliação do estado ácido-básico em recém-nascidos. As amostras venosas poderiam ser usadas de forma serial, para monitorizar tendências ao longo do tempo.

Agreement and correlation of pH, bicarbonate, base excess and lactate measurements in venous and arterial blood of premature and term infants.

BACKGROUND AND OBJECTIVES: Determine the extent of agreement and correlation between arterial samples and venous (obtained from a venous umbilical catheter), with respect to measurements of pH, bicarbonate, base excess and lactate, in critically ill term and premature newborns. METHODS: Arterial blood samples (0.5-1 mL) were obtained for gas analysis by radial artery puncture, and, within the limit of 5 minutes, samples were obtained from venous umbilical catheters. Bland-Altman plots were used to depict agreement between arterial and venous measurements. Limits of agreement were defined as the mean difference ± 2SD (Standard Deviation). Correlation was assessed by Pearson's method. RESULTS: A hundred and six samples (53 pairs) were taken from 53 patients for analysis of bicarbonate, pH and base excess. Lactate was analyzed in 49 pairs of samples. Differences were within the limits of agreement in 94.3% of pairs of samples for pH, and the same percentage was observed for bicarbonate. There was agreement in 96.2% of pairs for base excess, and in 91.8% for lactate. Mean differences were 0.03 units for pH, -1.2 mmol/L for bicarbonate, -0.24 mmol/L for base excess and 0.33 mmol/L for lactate. Pearson's correlation coefficients (r) were 0.87 for pH, 0.76 for bicarbonate, 0.86 for base excess and 0.95 for lactate. CONCLUSIONS: Although single venous values cannot be used as equivalent to arterial for assessing acid base status in newborns, venous blood samples can be used serially for monitoring trends over time.