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.

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.

Treatment of plastic bronchitis in acute chest syndrome of sickle cell disease with intratracheal rhDNase.

Plastic bronchitis, a condition associated with widespread mucous plugging of the tracheobronchial tree, is an increasingly recognised bronchoscopic finding in acute chest syndrome of sickle cell disease. Removal of casts by bronchoscopy is technically challenging. We describe a child with acute chest syndrome where bronchoscopic removal of extensive tracheobronchial plastic casts was facilitated by intratracheal rhDNase.

Incidence of hyponatraemia and hyponatraemic seizures in severe respiratory syncytial virus bronchiolitis.

AIM: To document the incidence and early evolution of hyponatraemia (serum sodium < 136 mmol l(-1)) associated with respiratory syncytial virus (RSV) bronchiolitis in infants requiring intensive care. METHODS: In a retrospective review over two winter seasons, 130 infants were admitted with confirmed RSV infection, of whom 39 were excluded because of either pre-existing risk factors for hyponatraemia: diuretic therapy (n = 14), cardiac disease (n = 10), renal disease (n = 2) or lack of admission sodium data (n = 13). RESULTS: The incidence of admission hyponatraemia in the remaining infants (median age 6 wk) was 33% (30/91), with 11% (10/91) exhibiting a serum sodium less than 130 mmol l(-1) . Hyponatraemic and normonatraemic infants were of a similar age (median 6 vs 7 wk, p = 0.82). With fluid restriction and diuretic therapy, the incidence of hyponatraemia at 48 h had decreased to 3.3%, odds ratio 0.07 (95% confidence interval 0.02-0.24, p < 0.001). Four infants (4%) suffered hyponatraemic seizures at admission (sodium 114-123 mmol l(-1)); three had received hypotonic intravenous fluids at 100-150 ml kg(-1) d(-1) before referral to intensive care. All four were managed successfully with hypertonic (3%) saline, followed by fluid restriction, resulting in immediate termination of seizure activity and normalization of serum sodium values over 48 h. CONCLUSION: Hyponatraemia is common among infants with RSV bronchiolitis presenting to intensive care. Neurological complications may occur and fluid therapy in vulnerable infants should be tailored to reduce this risk.

Hypoalbuminaemia in critically ill children: incidence, prognosis, and influence on the anion gap.

AIMS: Hypoalbuminaemia has significance in adult critical illness as an independent predictor of mortality. In addition, the anion gap is predominantly due to the negative charge of albumin, thus hypoalbuminaemia may lead to its underestimation. We examine this phenomenon in critically ill children, documenting the incidence, early evolution, and prognosis of hypoalbuminaemia (<33 g/l), and quantify its influence on the anion gap. METHODS: Prospective descriptive study of 134 critically ill children in the paediatric intensive care unit (ICU). Paired arterial blood samples were taken at ICU admission and 24 hours later, from which blood gases, electrolytes, and albumin were measured. The anion gap (including potassium) was calculated and then corrected for albumin using Figge's formula. RESULTS: The incidence of admission hypoalbuminaemia was 57%, increasing to 76% at 24 hours. Neither admission hypoalbuminaemia, nor extreme hypoalbuminaemia (<20 g/l) predicted mortality; however, there was an association with increased median ICU stay (4.9 v 3.6 days). After correction for albumin the incidence of a raised anion gap (>18 mEq/l) increased from 28% to 44% in all samples (n = 263); this discrepancy was more pronounced in the 103 samples with metabolic acidosis (38% v 73%). Correction produced an average increase in the anion gap of 2.7 mEq/l (mean bias), with limits of agreement of +/-3.7 mEq/l. CONCLUSION: Admission hypoalbuminaemia is common in critical illness, but is not an independent predictor of mortality. However, failure to correct the anion gap for albumin may underestimate the true anion gap, producing error in the interpretation of acid-base abnormalities. This may have treatment implications.

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.

A comparison of three scoring systems for mortality risk among retrieved intensive care patients.

AIMS: To assess the impact of two paediatric intensive care unit retrieval teams on the performance of three mortality risk scoring systems: pre-ICU PRISM, PIM, and PRISM II. METHODS: A total of 928 critically ill children retrieved for intensive care from district general hospitals in the south east of England (crude mortality 7.8%) were studied. RESULTS: Risk stratification was similar between the two retrieval teams for scores utilising data primarily prior to ICU admission (pre-ICU PRISM, PIM), despite differences in case mix. The fewer variables required for calculation of PIM resulted in complete data collection in 88% of patients, compared to pre-ICU PRISM (24%) and PRISM II (60%). Overall, all scoring systems discriminated well between survival and non-survival (area under receiver operating characteristic curve 0.83-0.87), with no differences between the two hospitals. There was a tendency towards better discrimination in all scores for children compared to infants and neonates, and a poor discrimination for respiratory disease using pre-ICU PRISM and PRISM II but not PIM. All showed suboptimal calibration, primarily as a consequence of mortality over prediction among the medium (10-30%) mortality risk bands. CONCLUSIONS: PIM appears to offer advantages over the other two scores in terms of being less affected by the retrieval process and easier to collect. Recalibration of all scoring systems is needed.

High-frequency oscillation in adolescents.

BACKGROUND: High-frequency oscillation (HFO) is a widely used lung-protective ventilatory strategy in paediatric and neonatal acute lung injury. Its safe and effective use has been hindered by inadequate recruitment of the lung during oscillation and, until recently, the lack of an adequately powered oscillator for use in adult practice. METHODS: We present data from three adolescents with severe acute respiratory distress syndrome (ARDS) who received HFO with the Sensormedics 3100B oscillator after failure of conventional mechanical ventilation. A manual recruitment manoeuvre was used in all patients prior to mechanical ventilation (conventional or HFO) and following tracheal suctioning or disconnection from the ventilator. Changes in oxygenation index were used to assess therapy. RESULTS: All patients showed at least a 25% reduction in oxygenation index within 2 h of HFO, with return to conventional ventilation after 27-65 h. CONCLUSIONS: We found HFO, in conjunction with manual recruitment and prone positioning, to be a well-tolerated mode of ventilation in adolescents with ARDS and who were unresponsive to conventional ventilation. Given this success we hope to renew interest in this method for adults with ARDS, together with concurrent use of manual recruitment.

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.

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.

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.