Evaluating the Impact of Cardiopulmonary Bypass Priming Fluids on Bleeding After Pediatric Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: Cardiopulmonary bypass (CPB) predisposes young children to coagulopathy. The authors evaluated possible effects of CPB priming fluids on perioperative bleeding in pediatric cardiac surgery. DESIGN: Meta-analysis and systematic review of previously published studies. SETTING: Each study was conducted in a surgical center or intensive care unit. PARTICIPANTS: Studies investigating patients <18 years without underlying hematologic disorders were included. INTERVENTIONS: The authors evaluated randomized controlled trials (RCTs) published between 1980 and 2020 on MEDLINE, EMBASE, PubMed, and CENTRAL databases. The primary outcome was postoperative bleeding; secondary endpoints included blood product transfusion, mortality, and safety. MEASUREMENTS AND MAIN RESULTS: Twenty eligible RCTs were analyzed, with a total of 1,550 patients and a median of 66 patients per study (range 20-200). The most frequently assessed intervention was adding fresh frozen plasma (FFP) to the prime (8/20), followed by albumin (5/20), artificial colloids (5/20), and blood-based priming solutions (3/20). Ten studies with 771 patients evaluated blood loss at 24 hours in mL/kg and were included in a meta-analysis. Most of them investigated the addition of FFP to the priming fluid (7/10). No significant difference was found between intervention and control groups, with a mean difference of -0.13 (-2.61 to 2.34), p = 0.92, I2 = 69%. Further study endpoints were described but their reporting was too heterogeneous to be quantitatively analyzed. CONCLUSIONS: This systematic review of current evidence did not show an effect of different CPB priming solutions on 24-hour blood loss. The analysis was limited by heterogeneity within the dataset regarding population, type of intervention, dosing, and the chosen comparator, compromising any conclusions.

Accuracy of the transpulmonary ultrasound dilution method for detection of small anatomic shunts.

The purpose of this study was to investigate the qualitative and quantitative accuracy of transpulmonary ultrasound dilution (UD) (COstatus™, Transonic Systems) for the detection of small anatomic shunts. It was a prospective, observational study in a multi-disciplinary pediatric intensive care unit. Seventy-three critically ill children (67 post cardiac surgery), with a median (IQR) age of 10 (3-50.3) months and a median (IQR) weight of 8 (3.43-13) kg were enrolled. Ultrasound dilution (UD) measurements were performed on patients within 1 h of undergoing two-dimensional echocardiography, which was used as the comparator technique. Shunt was diagnosed by characteristic changes on the UD curve shape, and was considered "test-positive" only if two or more measurements suggested the presence of the shunt. The UD technology also provided an estimate of pulmonary to systemic blood flow ratio (Qp:Qs). 12/73 (16.4 %) patients had a shunt identified by both UD and echocardiography. The overall accuracy (95 % CI) was 86.1 % (75.6-96.6 %), with a sensitivity of 85.7 % (57.2-98.2 %) and specificity of 86.4 % (75.0-94.0 %). The estimated Qp:Qs ranged from 0.7 to 1.4, which was consistent qualitatively with the echocardiographic findings on color flow doppler. Shunt was detected by UD alone in eight children; six of these had clinical conditions known to compromise dilution curve analysis (valve regurgitation, asymmetric pulmonary blood flow). Shunt was detected by echocardiography alone in two children; in both cases the shunt was tiny. UD is an accurate method for the detection of small anatomical shunts, both qualitatively and quantitatively.

Enteral absorption and haemodynamic response of clonidine in infants post-cardiac surgery.

BACKGROUND: Clonidine is a useful analgesic-sedative agent; however, few data exist regarding its use in infants after congenital heart disease surgery. We thus aimed to assess the absorption and safety of enterally administered clonidine in this setting. METHODS: Sixteen infants (median age 6.7 months) received a single nasogastric dose of 3 µg kg(-1) clonidine 2-6 h after surgery. Blood samples were obtained at seven time intervals (up to 480 min). Plasma concentration profiles were obtained, and then pooled with a previous study (137 samples, 30 infants) for estimation of population pharmacokinetic parameters (NONMEM version 7.2). RESULTS: Enteral absorption showed considerable inter-individual variability, with clonidine Cmax ranging from 0.15 to 1.55 ng ml(-1) (median 0.73), and Tmax from 12 to 478 min (median 190). Although therapeutic sedative plasma concentrations were achieved in 94% of patients, only half had attained this by 70 min post-dose. Patients who did not receive inotropes exhibited a positive association between cumulative morphine dose and Tmax (interaction effect P=0.03); this was not seen among those receiving inotropes. The haemodynamic profile was favourable; few patients required fluid boluses, and this bore no relationship to plasma clonidine concentration. Population pharmacokinetic parameter estimation yielded results similar to previous paediatric studies: clearance 13.7 litre h(-1) 70 kg(-1) and Vd 181 litre 70 kg(-1). CONCLUSIONS: Early postoperative enteral clonidine produces favourable haemodynamic profiles and therapeutic plasma concentrations in the majority of cardiac surgical infants; however, the time to achieve this can be erratic. Thus, parenteral administration may be preferable if rapid analgo-sedative effects are needed.

Pressure recording analytical method for measuring cardiac output in critically ill children: a validation study.

BACKGROUND: Pressure recording analytical method (PRAM) is a novel, arterial pulse contour-based method for measuring cardiac output (CO). Validation studies of PRAM in children are few, and have not assessed both absolute accuracy and ability to track changes in CO across a broad case mix. We aimed to compare CO as measured by PRAM with that using a transpulmonary dilution method in a cohort of critically ill children. METHODS: Forty-eight, mechanically ventilated children with a median (inter-quartile) weight of 10.7 (5.5-15) kg with arterial and central venous catheters in situ were studied. CO was measured simultaneously using PRAM and the comparator method, transpulmonary ultrasound dilution (UD). Measurements were repeated before and after therapeutic interventions that were intended to augment CO (e.g. fluid bolus). RESULTS: In total, 210 paired measurements were compared. The mean (sd) CO was 1.9 (1.2) litre min(-1) with UD when compared with 1.92 (0.5) litre min(-1) using PRAM. The mean bias was 0.02 litre min(-1) with wide limits of agreement: ± 2.21 litre min(-1), giving a percentage error of 116%. The concordance between PRAM and UD for measuring changes in CO was also poor, with only 37% of measurements falling within the pre-defined polar plot limits of ±30°. CONCLUSIONS: There is an unacceptably poor agreement between UD and PRAM. We do not recommend the use of PRAM for measuring CO in critically ill children with the current algorithm.

Soluble Fas may be a proinflammatory marker after cardiopulmonary bypass in children.

OBJECTIVES: Ischemia-reperfusion injury after cardiopulmonary bypass is known to provoke an inflammatory response, which can be attenuated with steroid pretreatment. Cardiopulmonary bypass is also known to stimulate apoptosis. Induction of the cellular apoptotic cascade occurs via interaction between two membrane receptors: Fas and Fas ligand. Both molecules also exist in soluble forms, whose significance remains undetermined; however, both may have a proinflammatory role. We aimed to document the temporal profile of soluble Fas and soluble Fas ligand after cardiopulmonary bypass and to investigate whether steroid pretreatment alters this response. METHODS: The study was of a non-randomized, non-blinded, prospective nature. Twenty-seven infants were monitored prospectively, of whom 13 received dexamethasone at induction of anesthesia. Soluble Fas, soluble Fas ligand, and interleukin 6 were measured from induction of anesthesia until 24 hours after admission to the intensive care unit. Data on clinical and laboratory variables were also collected at the same time intervals. RESULTS: As expected, dexamethasone pretreatment attenuated interleukin 6 release and the clinical systemic inflammatory response after bypass. Soluble Fas showed a remarkably similar profile to interleukin 6, in terms of temporal release and attenuation with steroids. There was also a correlation between maximum soluble Fas and markers of capillary leak (colloid requirement and drain loss). Conversely, soluble Fas ligand release was unchanged by cardiopulmonary bypass and steroid administration. However, patients with higher soluble Fas ligand levels exhibited a more dramatic drop and delayed recovery in monocyte count, consistent with the role of this molecule in apoptosis. CONCLUSIONS: Release of soluble Fas and soluble Fas ligand follows a markedly different temporal profile after cardiopulmonary bypass. The similarity between soluble Fas and interleukin 6, together with the attenuation of both with steroids, may suggest a role for soluble Fas as a proinflammatory marker.

Are transoesophageal Doppler parameters a reliable guide to paediatric haemodynamic status and fluid management?

OBJECTIVE: Transoesophageal Doppler (TOD) has been used in adults to optimise left ventricular filling on the basis of the waveform parameters. We wished to see if a similar relationship exists in children, specifically: (a) whether change in thermodilution stroke volume (SV) following a fluid bolus corresponded to change in Doppler stroke distance, Doppler corrected flow time (FTc), or central venous pressure (CVP); (b) whether a response to fluid challenge (defined as an increase in SV of greater than 10%) can be predicted on the basis of an absolute value for FTc or CVP prior to fluid bolus; and (c) the relationship between FTc and systemic vascular resistance index. DESIGN: Prospective, comparison study. SETTING: Sixteen-bed paediatric intensive care unit of a university hospital. PATIENTS: Ninety-four ventilated children were studied, median (range) age 25 months (4 days- 16 years). Diagnoses included: post-cardiac surgery (n = 58), sepsis/multi-organ failure (n = 29), respiratory disease (n = 5), and other (n = 2). INTERVENTIONS: A 4-MHz, 5.5-mm diameter, flexible TOD probe was placed when patients were haemodynamically stable. Five consecutive measurements of stroke distance and FTc were made and averaged, concurrently with five SV measurements by femoral artery thermodilution. SV was then augmented by administration of fluid (10 ml/kg), and haemodynamic recordings were repeated. MEASUREMENTS AND MAIN RESULTS: The median (range) SV was 17 ml (2-64 ml). The median coefficients of variation were 3.9 % for SV, 3.5 % for stroke distance, and 3.1% for FTc. Changes in SV were accurately tracked by changes in stroke distance (mean bias 1.8 %, limits of agreement +/- 17%), but not by FTc or CVP. FTc was weakly inversely correlated with systemic vascular resistance (r = -0.15, P < 0.05). Among non-cardiac patients (n = 36), the optimal FTc that predicted an improvement in SV following fluid bolus was 0.394 s (area under ROC curve 0.756), giving a sensitivity of 90 %, specificity of 62 %, positive predictive value of 47 %, and a negative predictive value of 94 %. CVP was a poor predictor for all patient groups. CONCLUSIONS: TOD stroke distance is able to follow changes in SV following fluid bolus amongst ventilated children, and can predict when further volume loading is unlikely to improve SV amongst general, but not cardiac ICU patients. CVP is a poor discriminator of volume status in this group of patients.

Evaluation of the 5-French saline paediatric gastric tonometer.

OBJECTIVE: To evaluate the paediatric 5-French (Fr) saline-filled gastric tonometer. DESIGN: (a) In vitro comparison of saline bath reference pCO2 with tonometric pCO2 measured by normal saline-filled and phosphate-buffered saline-filled 5-Fr tonometers, and by a recirculating gas tonometer. ( b) In vivo comparison of gastric intramucosal pCO2i, measured by normal saline-filled 5-Fr tonometer (NST) and simultaneously by recirculating gas tonometer (RGT) in ten paediatric intensive care patients. (c) In vivo comparison of pCO2i measured simultaneously by 2 NST 5-Fr tonometers, before and after enteral feeding, in ten paediatric intensive care patients. MEASUREMENTS AND MAIN RESULTS: (a) Twenty consecutive measurements of pCO2 were made at constant reference pCO2 of 19, 38, 56, and 75 mmHg (2.5, 5.0, 7.5, and 10.0 kPa), respectively. The NST tonometer underestimated reference pCO2 by mean bias (limits of agreement) of 58% (20%), and the phosphate-buffered saline-filled tonometer by 6% (26%). The RGT showed mean bias 5.7% with narrow limits of agreement (1.5%). (b) In 50 paired (NST vs. RGT) in vivo measurements over pCO2i range 23-73 mmHg (3.0-9.7 kPa), the NST underestimated RGT pCO2i by a mean bias of 10 mmHg (1.3 kPa), with limits of agreement +/-10 mmHg (1.5 kPa). This resulted in NST consistently overestimating pHi and underestimating pCO2 gap (both P < 0.001). (c) One hundred simultaneous paired NST measurements were assessed (50 without, and 50 with enteral feeding). The mean biases (limits of agreement) were identical in the fasted and fed states 0.4+/-6 mmHg, with no difference between the fed and fasting states (P = 0.7). CONCLUSIONS: There are inherent problems in the methodology of saline tonometry, which adversely affect the accuracy and reliability of the 5-Fr paediatric gastric tonometer in comparison to recirculating gas tonometry.

Clinical validation of cardiac output measurements using femoral artery thermodilution with direct Fick in ventilated children and infants.

OBJECTIVE: To validate clinically cardiac output (CO) measurements using femoral artery thermodilution in ventilated children and infants by comparison with CO estimated from the Fick equation via a metabolic monitor. DESIGN: Prospective, comparison study. SETTING: Paediatric intensive care unit of a university hospital. PATIENTS: 24 ventilated infants and children, aged 0.3 to 175 months (median age 19 months). INTERVENTIONS: Oxygen consumption measurements were made and averaged over a 5-min period, at the end of which arterial and mixed venous blood samples were taken and oxygen saturations measured by co-oximetry, with CO being calculated using the Fick equation. Over this 5-min period, five sets of femoral arterial thermodilution (FATD) measurements were made and averaged. One comparison of CO values was made per patient. RESULTS: Mean Fick CO was 2.55 l/min (range 0.24 to 8.71 l/min) and mean FATD CO was 2.51 l/min (range 0.28-7.96 l/min). The mean bias was 0.03 l/min (95% confidence interval -0.07 to 0.14 l/min), with limits of agreement of -0.45 to 0.52 l/min. When indexed to body surface area, the mean Fick cardiac index became 3.51 l/min per m2 (1.52-6.98 l/min per m2) and mean FATD 3.49 l/min per m2 (1.74-6.84 l/min per m2). The mean bias was 0.02 l/min per m2 (95% confidence interval -0.11 to 0.15 l/min per m2) with limits of agreement of-0.57 to 0.61 l/min per m2. The mean FATD coefficient of variation was 5.8% (SEM 0.5%). CONCLUSIONS: FATD compares favourably with Fick derived CO estimates in infants and children and may represent an advance in haemodynamic monitoring of critically ill children.

The value of the chloride: sodium ratio in differentiating the aetiology of metabolic acidosis.

OBJECTIVE: Stewart's physicochemical approach to acid-base balance defines the aetiology of a metabolic acidosis by quantifying anions of tissue acids (TA), which consist of unmeasured anions (UMA) and/or lactate. We hypothesised that an increase in TA during metabolic acidosis would lead to a compensatory fall in the plasma chloride (Cl) relative to sodium (Cl:Na ratio) in order to preserve electro-neutrality. Thus, the Cl:Na ratio could be used as a simple alternative to the anion gap in identifying raised TA. PATIENTS: Two hundred and eighty two consecutive patients who were admitted to our Paediatric Intensive Care were enrolled in the study. INTERVENTIONS: We obtained 540 samples (admission n = 282, 24 h n = 258) for analysis of blood chemistry, lactate and quantification of TA and UMA. Samples were subgrouped into those with metabolic acidosis (standard bicarbonate < 22 mmol/l) either with or without increased UMA (> 3 mEq/l). MEASUREMENTS AND RESULTS: Metabolic acidosis occurred in 46% of samples, of which 52.3% (120/230) had increased UMA. The dominant component of TA was UMA rather than lactate, and these two components did not always rise in tandem. Our hypothesis of relative hypochloraemia was supported by a lower Cl:Na ratio (P < 0.0001) but not a lower absolute Cl (P = 0.5) in the acidotic subgroup with raised UMA, and by the inverse relationship between TA and the Cl:Na ratio. (coefficient of determination (r2) = 0.37, P < 0.0001). The best discriminator for the presence of raised TA was the albumin-corrected anion gap (AGcorr), however, this could not track changes in TA with clinical accuracy. The Cl:Na ratio discriminated reasonably well, a ratio of < 0.75 identified TA (positive predictive value (PPV) 88%) with a likelihood ratio (LR) similar to the AG (7.8 vs7.4). Conversely, a high ratio (> 0.79) excluded TA (PPV 81%, LR 4.5). Base deficit (BD) and lactate performed poorly. CONCLUSION: In metabolic acidosis due to TA, plasma Cl concentration decreases relative to sodium. The Cl:Na ratio is a simple alternative to the AG for detecting TA in this setting.

Cardiac output measured by lithium dilution and transpulmonary thermodilution in patients in a paediatric intensive care unit.

OBJECTIVE: To compare the results of cardiac output measurements obtained by lithium dilution and transpulmonary thermodilution in paediatric patients. DESIGN: A prospective study. SETTING: Paediatric intensive care unit in a university teaching hospital. PATIENTS: Twenty patients (age 5 days-9 years; weight 2.6-28.2 kg) were studied. INTERVENTIONS: Between two and four comparisons of lithium dilution cardiac output (LiDCO) and transpulmonary thermodilution (TPCO) were made in each patient. MEASUREMENTS AND RESULTS: Results from three patients were excluded: in one patient there was an unsuspected right-to-left shunt, in two patients there was a problem with blood sampling through the lithium sensor. There were 48 comparisons of LiDCO and TPCO in the remaining 17 patients over a range of 0.4-6 l/min. The mean of the differences (LiDCO-TPCO) was -0.1 +/- 0.3 (SD) l/min. Linear regression analysis gave LiDCO = 0.11 + 0.90 x TPCO l/min (r2 = 0.96). There were no adverse effects in any patient. CONCLUSIONS: These results suggest that the LiDCO method can be used to provide safe and accurate measurement of cardiac output in paediatric patients. The method is simple and quick to perform, requiring only arterial and venous catheters, which will already have been inserted for other reasons in these patients.

Safety of nicotine replacement therapy in critically ill smokers: a retrospective cohort study.

PURPOSE: Nicotine replacement therapy (NRT) has been used to ameliorate nicotine withdrawal in the intensive care unit (ICU). Previous cohort studies have suggested an increased mortality with NRT use: methodological problems may call into question the validity of these findings. We undertook a retrospective cohort study to determine if NRT use was associated with adverse outcomes. METHODS: This retrospective cohort study was conducted in a 30-bed, university affiliated, teaching hospital ICU. RESULTS: We identified 423 smokers admitted over 2 years, of whom 73 received transdermal NRT. Cox proportional hazard regression models, with NRT modelled as a time-varying covariate, were used to test the hypothesis that NRT was associated with an altered ICU or hospital mortality. A second analysis utilized propensity scores. The unadjusted ICU and hospital mortalities were lower for the NRT group; although both differences were non-significant. The Cox models showed that, after adjustment for APACHE risk, age, sex and alcohol use, risk associated with NRT administration was not statistically different than non-administration for both ICU (hazard ratio 0.50, [95 % CI 0.20-1.24], p = 0.14) and hospital (hazard ratio 0.95, [95 % CI 0.52-1.75], p = 0.88) mortality. Similar findings occurred with the propensity matched analysis. CONCLUSION: We were unable to demonstrate any harm associated with NRT, with the ICU model actually trending towards benefit. We conclude that a randomised, blinded, placebo controlled trial is required to assess adequately the safety and efficacy of NRT as a treatment in critically ill smokers.

Should parents accompany critically ill children during inter-hospital transport?

BACKGROUND: Parental accompaniment during inter-hospital transportation (retrieval) of critically ill children is not commonplace in the United Kingdom. METHODS: A three month pilot of parental accompaniment was undertaken in 2002 (143 retrievals), after which time the policy was adopted as standard practice. A follow up audit was performed in 2004 (136 retrievals). RESULTS: Findings were remarkably consistent between the two periods. Staff perceived little or no added stress during the majority of transfers (96% in 2002, 98% in 2004), and felt able to perform medical interventions without hindrance (98% in 2002, 100% in 2004). There was good agreement between medical and nursing staff regarding perception of stress and ability to perform interventions (phi statistic 0.57 to 1.00). Adverse events occurred during 11 (3.9%) retrievals; six of these involved a parent exclusively. Stress tended to be associated with adverse events or parental behaviour rather than disease acuity. Staff vetoed the offer of accompaniment on 11 occasions, for a variety of reasons. The majority of parents found the experience safe, beneficial, and perceived a reduction in stress as a result. These data may inform other retrieval services who are considering adopting a similar policy.

Monitoring cardiac function in intensive care.

Systolic cardiac function results from the interaction of four interdependent factors: heart rate, preload, contractility, and afterload. Heart rate can be quantified easily at the bedside, while preload estimation has traditionally relied on invasive pressure measurements, both central venous and pulmonary artery wedge. These have significant clinical limitations; however, adult literature has highlighted the superiority of several novel preload measures. Measurement of contractility and afterload is difficult; thus in clinical practice the bedside assessment of cardiac function is represented by cardiac output. A variety of techniques are now available for cardiac output measurement in the paediatric patient. This review summarises cardiac function and cardiac output measurement in terms of methodology, interpretation, and their contribution to the concepts of oxygen delivery and consumption in the critically ill child.

Use of transesophageal Doppler ultrasonography in ventilated pediatric patients: derivation of cardiac output.

OBJECTIVE: To ascertain if cardiac output (CO) could be derived from blood flow velocity measured in the descending aorta of ventilated children by transesophageal Doppler ultrasonography (TED) without the need for direct aortic cross sectional area measurement, and to evaluate the ability of TED to follow changes in CO when compared with femoral artery thermodilution. DESIGN: Prospective, comparison study. SETTING: A 16-bed pediatric intensive care unit of a university hospital. PATIENTS: A total of 100 ventilated infants and children aged 4 days to 18 yrs (median age, 27 months). Diagnoses included postcardiac surgery (n = 58), sepsis/multiple organ failure (n = 32), respiratory disease (n = 5), and other (n = 5). A total of 55 patients were receiving inotropes or vasodilators. INTERVENTIONS: When patients were hemodynamically stable, a TED probe was placed into the distal esophagus to obtain optimal signal, and minute distance (MD) was recorded. Five consecutive MD measurements were made concurrently with five femoral artery thermodilution measurements, and the concurrent measurements were averaged. CO was then manipulated by fluid administration or inotrope adjustment, and the readings were repeated. MEASUREMENTS AND MAIN RESULTS: Femoral artery thermodilution CO ranged from 0.32 to 9.19 L/min, (median, 2.46 L/min), and encompassed a wide range of high and low flow states. Theoretical consideration revealed the optimal TED estimate for CO to be (MD x patient height2 x 10(-7)). Linear regression analysis yielded a power function model such that: estimated CO = 1.158 x (MD x height2 x 10(-7))(0.785), r2 = 0.879, standard error of the estimate = 0.266. Inclusion of a correction factor for potential changes in aortic cross-sectional area with hypo- and hypertension did not appreciably improve the predictive value of the model. MD was able to follow percentage changes in CO, giving a mean bias of 0.87% (95% confidence interval -0.85% to 2.59%), and limits of agreement of +/- 16.82%. The median coefficient of variation for MD was 3.3%. CONCLUSIONS: TED provides a clinically accurate estimate of CO across the entire pediatric age range and is able to follow changes in CO.

Capillary refill and core-peripheral temperature gap as indicators of haemodynamic status in paediatric intensive care patients.

OBJECTIVES: Capillary refill time is an important diagnostic adjunct in the acute resuscitation phase of the shocked child. This study assesses its relation to commonly measured haemodynamic parameters in the postresuscitation phase when the child has reached the intensive care unit, and compares this with core-peripheral temperature gap. METHODS: Ninety standardised measurements of capillary refill time were made on 55 patients, who were divided into postcardiac surgery (n = 27), and general (n = 28), most of whom had septic shock (n = 24). A normal capillary refill time was defined as < or = 2 seconds. Measured haemodynamic variables included: cardiac index, central venous pressure, systemic vascular resistance index, stroke volume index (SVI), and blood lactate. Seventy measurements were made on patients while being treated with inotropes or vasodilators. RESULTS: Capillary refill time and temperature gap both correlated poorly with all haemodynamic variables among post-cardiac surgery children. For general patients, capillary refill time was related to SVI and lactate; temperature gap correlated poorly with all variables. General patients with a prolonged capillary refill time had a lower median SVI (28 v 38 ml/m2) but not a higher lactate (1.7 v 1.1 mmol/l). A capillary refill time of > or = 6 seconds had the best predictive value for a reduced SVI. CONCLUSION: Among ventilated, general intensive care patients, capillary refill time is related weakly to blood lactate and SVI. A normal value for capillary refill time of < or = 2 seconds has little predictive value and might be too conservative for this population; septic shock.

Procalcitonin and cytokine levels: relationship to organ failure and mortality in pediatric septic shock.

BACKGROUND: Procalcitonin (PCT), a marker of bacterial sepsis, may also act as a mediator of the inflammatory response to infection, and thus influence outcome. OBJECTIVE: To investigate the relationship between PCT, interleukin (IL)-10, tumor necrosis factor (TNF), organ failure, and mortality in pediatric septic shock. DESIGN: Prospective observational study. SETTING: A 16-bed pediatric intensive care unit of a university hospital. PATIENTS: A total of 75 children with septic shock having a median age of 43.1 months (range, 0.1-192 months). Children who had received antibiotics for >24 hrs were excluded. A total of 37 patients (49%) had meningococcal disease, and 72 patients (96%) required mechanical ventilation. INTERVENTIONS: The pediatric risk of mortality (PRISM) score, multiple organ system failure (MOSF) score, duration of ventilation, length of ICU stay, and outcome were recorded. PCT, IL-10, and TNF were measured at admission to the intensive care unit. Sequential PCT levels were available at 0 hrs and 24 hrs in 39 patients (52%). RESULTS: Observed mortality was 21/75 (28%). Data are median (range). The admission PCT (p = .0002) and TNF levels (p = .0001) were higher in children with higher MOSF scores. In survivors and nonsurvivors, the admission PCT was 82 ng/mL vs. 273 ng/mL (p = .03), IL-10 was 62 pg/mL vs. 534 pg/mL (p = .03), and TNF was 76 pg/mL vs. 480 pg/mL (p = .001), respectively. Area under the mortality receiver operating characteristic curve was 0.73 for PCT, 0.67 for IL-10, and 0.76 for TNF, compared with 0.83 for the PRISM score. Of 39 children, 16 (41%) with sequential PCT measurements showed no fall in PCT after 24 hrs treatment. These children had higher admission levels of IL-10 (p = .03), and TNF (p = .03) compared with children who demonstrated a subsequent fall in PCT. Although the former did not have a higher median PRISM (p = .28) or MOSF score (p = .19), observed mortality was 44% (7 of 16) compared with 9% (2 of 23) (p = .02). CONCLUSION: The admission PCT, like TNF and IL-10, is related to the severity of organ failure and mortality in children with septic shock. A fall in PCT after 24 hrs of treatment may have favorable prognostic significance.