Shane M. Tibby

Diagnostic markers of infection: comparison of procalcitonin with C reactive protein and leucocyte count

BACKGROUND Procalcitonin has been advocated as a marker of bacterial infection. OBJECTIVE To evaluate diagnostic markers of infection in critically ill children, comparing procalcitonin with C reactive protein and leucocyte count in a paediatric intensive care unit (PICU). METHODS Procalcitonin, C reactive protein, and leucocyte count were measured in 175 children, median age 16 months, on admission to the PICU. Patients were classified as: non-infected controls (43); viral infection (14); localised bacterial infection without shock (25); bacterial meningitis/encephalitis (10); or septic shock (77). Six children with “presumed septic shock” (without sufficient evidence of infection) were analysed separately. Optimum sensitivity, specificity, predictive values, and area under the receiver operating characteristic (ROC) curve were evaluated. RESULTS Admission procalcitonin was significantly higher in children with septic shock (median 94.6; range 3.3–759.8 ng/ml), compared with localised bacterial infection (2.9; 0–24.3 ng/ml), viral infection (0.8; 0–4.4 ng/ml), and non-infected controls (0; 0–4.9 ng/ml). Children with bacterial meningitis had a median procalcitonin of 25.5 (7.2–118.4 ng/ml). Area under the ROC curve was 0.96 for procalcitonin, 0.83 for C reactive protein, and 0.51 for leucocyte count. Cut off concentrations for optimum prediction of septic shock were: procalcitonin > 20 ng/ml and C reactive protein > 50 mg/litre. A procalcitonin concentration > 2 ng/ml identified all patients with bacterial meningitis or septic shock. CONCLUSION In critically ill children the admission procalcitonin concentration is a better diagnostic marker of infection than C reactive protein or leucocyte count. A procalcitonin concentration of 2 ng/ml might be useful in differentiating severe bacterial disease in infants and children.

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.

Clinicians’ abilities to estimate cardiac index in ventilated children and infants

OBJECTIVES To evaluate the ability of clinicians involved in the provision of paediatric intensive care to estimate cardiac index in ventilated children, based on physical examination and clinical and bedside laboratory data. METHODS Clinicians were exposed to all available haemodynamic and laboratory data for each patient, allowed to make a physical examination, and asked to first categorise cardiac index as high, high to normal, low to normal, or low, and then to quantify this further with a numerical estimate. Cardiac index was measured simultaneously by femoral artery thermodilution (coefficient of variation 5.37%). One hundred and twelve estimates were made by 27 clinicians on 36 patients (median age 34.5 months). RESULTS Measured cardiac index ranged from 1.39 to 6.84 l/min/m2. Overall, there was poor correlation categorically (κ statistic 0.09, weighted κ 0.169) and numerically (r = 0.24, 95% confidence interval 0.06 to 0.41 ), although some variation was seen among the various levels of seniority. CONCLUSION Assuming that objective measurement, and hence manipulation, of haemodynamic variables may improve outcome, these findings support the need for a safe, accurate, and repeatable technique for measurement of cardiac index in children who are critically ill.

Adrenal insufficiency in septic shock

BACKGROUND Functional adrenal insufficiency has been documented in critically ill adults. OBJECTIVE To document the incidence of adrenal insufficiency in children with septic shock, and to evaluate its effect on catecholamine requirements, duration of intensive care, and mortality. SETTING Sixteen-bed paediatric intensive care unit in a university hospital. METHODS Thirty three children with septic shock were enrolled. Adrenal function was assessed by the maximum cortisol response after synthetic adrenocorticotropin stimulation (short Synacthen test). Insufficiency was defined as a post-Synacthen cortisol increment < 200 nmol/l. RESULTS Overall mortality was 33%. The incidence of adrenal insufficiency was 52% and children with adrenal insufficiency were significantly older and tended to have higher paediatric risk of mortality scores. They also required higher dose vasopressors for haemodynamic stability. In the survivor group, those with adrenal insufficiency needed a longer period of inotropic support than those with normal function (median, 3 v 2 days), but there was no significant difference in duration of ventilation (median, 4 days for each group) or length of stay (median, 5 v 4 days). Mortality was not significantly greater in children with adrenal insufficiency than in those with adequate adrenal function (6 of 17v 5 of 16, respectively). CONCLUSION Adrenal insufficiency is common in children with septic shock. It is associated with an increased vasopressor requirement and duration of shock.

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 ⩽ 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 postcardiac 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 (28v 38 ml/m2) but not a higher lactate (1.7 v 1.1 mmol/l). A capillary refill time of ⩾ 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 ⩽ 2 seconds has little predictive value and might be too conservative for this population; septic shock

Therapeutic hypothermia after cardiac arrest: a retrospective comparison of surface and endovascular cooling techniques.

OBJECTIVES Therapeutic hypothermia (32-34 degrees C) is recommended for comatose survivors of cardiac arrest; however, the optimal technique for cooling is unknown. We aimed to compare therapeutic hypothermia using either surface or endovascular techniques in terms of efficacy, complications and outcome. DESIGN Retrospective cohort study. SETTING Thirty-bed teaching hospital intensive care unit (ICU). PATIENTS All patients (n=83) undergoing therapeutic hypothermia following cardiac arrest over a 2.5-year period. The mean age was 61+/-16 years; 88% of arrests occurred out of hospital, and 64% were ventricular fibrillation/tachycardia. INTERVENTIONS Therapeutic hypothermia was initiated in the ICU using iced Hartmanns solution, followed by either surface (n=41) or endovascular (n=42) cooling; choice of technique was based upon endovascular device availability. The target temperature was 32-34 degrees C for 12-24 h, followed by rewarming at a rate of 0.25 degrees Ch(-1). MEASUREMENTS AND MAIN RESULTS Endovascular cooling provided a longer time within the target temperature range (p=0.02), less temperature fluctuation (p=0.003), better control during rewarming (0.04), and a lower 48-h temperature load (p=0.008). Endovascular cooling also produced less cooling-associated complications in terms of both overcooling (p=0.05) and failure to reach the target temperature (p=0.04). After adjustment for known confounders, there were no differences in outcome between the groups in terms of ICU or hospital mortality, ventilator free days and neurological outcome. CONCLUSION Endovascular cooling provides better temperature management than surface cooling, as well as a more favorable complication profile. The equivalence in outcome suggested by this small study requires confirmation in a randomized trial.

The Relationship Among Thromboelastography, Hemostatic Variables, and Bleeding After Cardiopulmonary Bypass Surgery in Children

BACKGROUND:Mediastinal bleeding is common after pediatric cardiopulmonary bypass (CPB) surgery. Thromboelastography (TEG®) may predict bleeding and provide insight into likely mechanisms. We aimed to (a) compare perioperative temporal profiles of TEG® and laboratory hemostatic variables between patients with significant hemorrhage (BLEED) and those without (CONTROL), (b) investigate the relationship between TEG® variables and routine hemostatic variables, and (c) develop a model for prediction of bleeding. METHODS:TEG® and laboratory hemostatic variables were measured prospectively at 8 predefined times for 50 children weighing <20 kg undergoing CPB. RESULTS:Patients who bled demonstrated different TEG® profiles than those who did not. This was most apparent after protamine administration and was partly attributable to inadequate heparin reversal, but was also associated with a significantly lower nadir in mean (SD) fibrinogen for the BLEED group compared with CONTROL group: 0.44 (0.18) and 0.71 (0.40) g/L, respectively (P = 0.01). Significant nonlinear relationships were found between the majority of TEG® and laboratory hemostatic variables. The strongest relationship was between the maximal amplitude and the platelet-fibrinogen product (logarithmic r2 = 0.71). Clot strength decreased rapidly when (a) fibrinogen concentration was <1 g/L, (b) platelets were <120 × 109/L, and (c) platelet-fibrinogen product was <100. A 2-variable model including the activated partial thromboplastin time at induction of anesthesia and TEG® mean amplitude postprotamine discriminated well for subsequent bleeding (C statistic 0.859). CONCLUSIONS:Hypofibrinogenemia and inadequate heparin reversal are 2 important factors contributing to clot strength and perioperative hemorrhage after pediatric CPB. TEG® may be a useful tool for predicting and guiding early treatment of mediastinal bleeding in this group.

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 × patient height2 × 10−7). Linear regression analysis yielded a power function model such that: estimated CO = 1.158 × (MD × height2 × 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.

Relationship Between Arterial Partial Oxygen Pressure After Resuscitation From Cardiac Arrest and Mortality in Children

Background— Observational studies in adults have shown a worse outcome associated with hyperoxia after resuscitation from cardiac arrest. Extrapolating from adult data, current pediatric resuscitation guidelines recommend avoiding hyperoxia. We investigated the relationship between arterial partial oxygen pressure and survival in patients admitted to the pediatric intensive care unit (PICU) after cardiac arrest. Methods and Results— We conducted a retrospective cohort study using the Pediatric Intensive Care Audit Network (PICANet) database between 2003 and 2010 (n=122 521). Patients aged <16 years with documented cardiac arrest preceding PICU admission and arterial blood gas analysis taken within 1 hour of PICU admission were included. The primary outcome measure was death within the PICU. The relationship between postarrest oxygen status and outcome was modeled with logistic regression, with nonlinearities explored via multivariable fractional polynomials. Covariates included age, sex, ethnicity, congenital heart disease, out-of-hospital arrest, year, Pediatric Index of Mortality-2 (PIM2) mortality risk, and organ supportive therapies. Of 1875 patients, 735 (39%) died in PICU. Based on the first arterial gas, 207 patients (11%) had hyperoxia (PaO2 ≥300 mm Hg) and 448 (24%) had hypoxia (PaO2 <60 mm Hg). We found a significant nonlinear relationship between PaO2 and PICU mortality. After covariate adjustment, risk of death increased sharply with increasing hypoxia (odds ratio, 1.92; 95% confidence interval, 1.80–2.21 at PaO2 of 23 mm Hg). There was also an association with increasing hyperoxia, although not as dramatic as that for hypoxia (odds ratio, 1.25; 95% confidence interval, 1.17–1.37 at 600 mm Hg). We observed an increasing mortality risk with advancing age, which was more pronounced in the presence of congenital heart disease. Conclusions— Both severe hypoxia and, to a lesser extent, hyperoxia are associated with an increased risk of death after PICU admission after cardiac arrest.

The strong ion gap predicts mortality in children following cardiopulmonary bypass surgery.

Objective: Stewart’s strong ion theory quantifies unmeasured tissue acids produced following hypoxia or hypoperfusion, by calculation of the strong ion gap. Our study objectives were as follows: a) to determine the 24-hr profile of the strong ion gap following cardiopulmonary bypass surgery; and b) to compare the prognostic value in terms of intensive care unit mortality of this variable with blood lactate. Design: Prospective, observational study. Setting: Tertiary pediatric intensive care unit. Patients: Eighty-five children following surgery for congenital heart disease. Interventions: None. Measurements and Main Results: Arterial blood samples for lactate and strong ion gap calculation were obtained at intensive care unit admission and at 24 hrs. A raised strong ion gap (>3 mEq/L) was present in 41.1% and 51.7% of admission and 24-hr samples, respectively, being elevated at both time points in 30.5%. Both the strong ion gap and lactate increased with surgical complexity, but neither was correlated with length of bypass (r = .13 and −.02) or aortic cross-clamp (r = .13 and .10). The crude mortality was 5.8% (5/85). Four of the five deaths were associated with a persistently elevated strong ion gap, in contrast to two with ongoing hyperlactatemia (>2 mmol/L). The admission strong ion gap (cutoff, >3.2 mEq/L) was superior to lactate (cutoff, >3.0 mmol/L) as a mortality predictor (area under receiver operating characteristic curve of 0.85 [95% confidence interval, 0.74–0.95] vs. 0.71 [95% confidence interval, 0.44–0.98], respectively). Conclusions: An elevated strong ion gap occurs commonly following bypass surgery and appears to be superior to lactate as a mortality predictor.