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Biomedical subjects

M Hatherill

Publications and source records attributed to M Hatherill.

At least 19 recordsLinked to original sources

Short-term mortality and implementation of antiretroviral treatment for critically ill HIV-infected children in a developing country.

OBJECTIVE: To describe the short-term outcome of critically ill HIV-infected children with access to highly active antiretroviral therapy (HAART) in a developing region. METHODS: Prospective observational study conducted in a paediatric teaching hospital in Cape Town, South Africa. All children admitted to the paediatric intensive care unit (PICU) with suspected HIV infection were screened. Data are n (%) with 95% confidence intervals. RESULTS: Sixty eight of 96 HIV antibody-positive children, median age 3 months, were confirmed HIV-infected. Predicted PICU mortality was 0.42. Fifty one children (75%; 95% CI 65 to 85%) survived to PICU discharge, but hospital survival was only 51% (95% CI 40 to 63%). Limitation of intervention (LOI) decisions were a factor in the majority of PICU and ward deaths. Twenty one PICU survivors (31%; 95% CI 20 to 42%) commenced HAART, and two children were already on treatment. Nineteen children (28%) were considered to be established on HAART after 1 month. Thirteen HIV-infected children (19%; 95% CI 10 to 28%), representing 25% (95% CI 14 to 37%) of all PICU survivors, and 68% (95% CI 48 to 89%) of those PICU survivors who were established on HAART remain well on treatment after median 350 days. CONCLUSION: The majority of HIV-infected children survived to discharge from PICU, but only half survived to hospital discharge. LOI decisions, usually made in PICU, directly influenced short-term survival and the opportunity to commence HAART. Although few critically ill HIV-infected children survived to become established on HAART, the long-term outcome of children on HAART is encouraging and warrants further investigation.

Antiretroviral Therapy, Highly Active↗

Hyperchloraemic metabolic acidosis following open cardiac surgery.

AIMS: To describe acid-base derangements in children following open cardiac surgery on cardiopulmonary bypass (CPB), using the Fencl-Stewart strong ion approach. METHODS: Prospective observational study set in the paediatric intensive care unit (PICU) of a university children's hospital. Arterial blood gas parameters, serum electrolytes, strong ion difference, strong ion gap (SIG), and partitioned base excess (BE) were measured and calculated on admission to PICU. RESULTS: A total of 97 children, median age 57 months (range 0.03-166), median weight 14 kg (range 2.1-50), were studied. Median CPB time was 80 minutes (range 17-232). Predicted mortality was 2% and there was a single non-survivor. These children showed mild metabolic acidosis (median standard bicarbonate 20.1 mmol/l, BE -5.1 mEq/l) characterised by hyperchloraemia (median corrected Cl 113 mmol/l), and hypoalbuminaemia (median albumin 30 g/l), but no significant excess unmeasured anions or cations (median SIG 0.7 mEq/l). The major determinants of the net BE were the chloride and albumin components (chloride effect -4.8 mEq/l, albumin effect +3.4 mEq/l). Metabolic acidosis occurred in 72 children (74%) but was not associated with increased morbidity. Hyperchloraemia was a causative factor in 53 children (74%) with metabolic acidosis. Three (4%) hyperchloraemic children required adrenaline for inotropic support, compared to eight children (28%) without hyperchloraemia. Hypoalbuminaemia was associated with longer duration of inotropic support and PICU stay. CONCLUSIONS: In these children with low mortality following open cardiac surgery, hypoalbuminaemia and hyperchloraemia were the predominant acid-base abnormalities. Hyperchloraemia was associated with reduced requirement for adrenaline therapy. It is suggested that hyperchloraemic metabolic acidosis is a benign phenomenon that should not prompt escalation of haemodynamic support. By contrast, hypoalbuminaemia, an alkalinising force, was associated with prolonged requirement for intensive care.

Acidosis↗

Evolution of an adenovirus outbreak in a multidisciplinary children's hospital.

OBJECTIVE: To describe the course of an evolving adenovirus outbreak in a multidisciplinary children's hospital with a high-risk patient population. METHODS: Observational study in a 280-bed university hospital during June 2002. Active case finding identified children with adenovirus infection. Data are median (interquartile range) or n (%). Adenovirus infection was diagnosed in 49 children, median age 12 months (4-33). RESULTS: New cases were diagnosed over 26 days and peaked on day 17 (n = 15). Total infected inpatients peaked on days 17-21 (n = 36). Twenty-three infections (47%) were community-acquired and 26 (53%) hospital-acquired. Thirty-three children (67%) had a coexistent high-risk condition. Median hospital stay before and after diagnosis was 9 days (3-18) and 9 days (4-29), respectively. Twenty-two children (45%) were admitted to PICU. Overall hospital mortality was 22% (n = 11) and mortality attributed to adenoviral disease 12% (n = 6). Hospital mortality was similar between community- and hospital-acquired infections (22% compared to 23%) (P = 1.0). Twenty children (41%) received intravenous immunoglobulin (IVIG). Children treated with IVIG had a longer hospital stay (median 40 days vs 14 days) than those who did not receive IVIG (P = 0.01). Neither PICU mortality (29% vs 12%), nor hospital mortality (35% vs 14%), differed significantly between IVIG treated and untreated children (P = 0.76 and P = 0.16, respectively). CONCLUSION: The rapid spread of hospital-acquired adenovirus underlines the importance of effective infection control measures. Despite nosocomial infection amongst high-risk patients, mortality was similar to that of community-acquired infection. Administration of immunoglobulin was not associated with demonstrable benefit. A prospective randomized trial would be required to resolve this issue.

Adenoviridae↗

HIV infection of undetermined origin during infancy.

The case histories of two children with horizontally acquired HIV infection are described. These children were diagnosed at a paediatric hospital in sub-Saharan Africa. Although the source(s) of infection was not identified, both children had had several contacts with the health service, experienced invasive procedures and ingested expressed milk from their own mothers during hospital admission. Health-care institutions, particularly those located in high HIV prevalence areas, must implement effective infection control measures to ensure that the risk of horizontal infection is minimized. Attention should be given to practices that are unique to each clinical discipline.

AIDS Serodiagnosis↗

Organophosphate poisoning complicated by a tachyarrhythmia and acute respiratory distress syndrome in a child.

A 9-year-old child presented with documented organophosphate insecticide poisoning. His course was initially complicated by a tachyarrhythmia with QT-interval prolongation that responded promptly to intravenous magnesium. However, following partial recovery, he developed progressive acute respiratory distress syndrome characterized by irreversible fibrosis and obliteration of the lung parenchyma.

Child↗

Presentation and outcome of severe anticholinesterase insecticide poisoning.

AIMS: To document the patterns of presentation and outcome of severe anticholinesterase insecticide poisoning in children requiring intensive care. METHODS: Retrospective case note review of all 5541 children admitted to the paediatric intensive care unit (PICU) of a university hospital during the 10 years from January 1990 to May 2000. Fifty four children (1%) with anticholinesterase insecticide poisoning were identified. Presenting features, route of exposure, treatment, complications, and mortality were recorded. Data were analysed by the Fisher's exact and Mann-Whitney tests. RESULTS: More children than expected were from a rural area (46% versus 25%). Decontamination occurred in 50% of children prior to PICU admission. Enteral exposure was most common (n = 27; 50%). Median pseudocholinesterase level was 185 IU/l (range 75-7404). Median total dose of atropine required to maintain mydriasis was 0.3 mg/kg (range 0.03-16.7) over a median of 10 hours (range 1-160). Complications included coma (31%), seizures (30%), shock (9%), arrhythmias (9%), and respiratory failure requiring ventilation (35%). No significant differences were detected in incidence of seizures, cardiac arrhythmias, respiratory failure, mortality, duration of ventilation, or PICU stay, according to route of exposure, or state of decontamination. Four children died (7%). Mortality was associated with the presence of a cardiac arrhythmia (likelihood ratio 8.3) and respiratory failure (likelihood ratio 3.3). CONCLUSION: The mortality and morbidity of severe anticholinesterase insecticide poisoning in childhood is not related to route of exposure, or to delay in decontamination. However, the presence of either a cardiac arrhythmia or respiratory failure is associated with a poor prognosis.

Adolescent↗

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.

Child↗

Correction of the anion gap for albumin in order to detect occult tissue anions in shock.

BACKGROUND: It is believed that hypoalbuminaemia confounds interpretation of the anion gap (AG) unless corrected for serum albumin in critically ill children with shock. AIM: To compare the ability of the AG and the albumin corrected anion gap (CAG) to detect the presence of occult tissue anions. METHODS: Prospective observational study in children with shock in a 22 bed multidisciplinary paediatric intensive care unit of a university childrenrsquo;s hospital. Blood was sampled at admission and at 24 hours, for acid-base parameters, serum albumin, and electrolytes. Occult tissue anions (lactate + truly "unmeasured" anions) were calculated from the strong ion gap. The anion gap ((Na + K) - (Cl + bicarbonate)) was corrected for serum albumin using the equation of Figge: AG + (0.25 x (44 - albumin)). Occult tissue anions (TA) predicted by the anion gap were calculated by (anion gap - 15 mEq/l). Optimal cut off values of anion gap were compared by means of receiver operating characteristic (ROC) curves. Ninety three sets of data from 55 children (median age 7 months, median weight 4.9 kg) were analysed. Data are expressed as mean (SD), and mean bias (limits of agreement). RESULTS: The incidence of hypoalbuminaemia was 76% (n = 42/55). Mean serum albumin was 25 g/l (SD 8). Mean AG was 15.0 mEq/l (SD 6.1), compared to the CAG of 19.9 mEq/l (SD 6.6). Mean TA was 10.2 mmol/l (SD 6.3). The AG underestimated TA with mean bias 10.2 mmol/l (4.1-16.1), compared to the CAG, mean bias 5.3 mmol/l (0.4-10.2). A clinically significant increase of TA >5 mmol/l was present in 83% (n = 77/93) of samples, of which the AG detected 48% (n = 36/77), and the CAG 87% (n = 67/77). Post hoc ROC analysis revealed optimal cut off values for detection of TA >5 mmol/l to be AG >10 mEq/l, and CAG >15.5 mEq/l. CONCLUSION: Hypoalbuminaemia is common in critically ill children with shock, and is associated with a low observed anion gap that may fail to detect clinically significant amounts of lactate and other occult tissue anions. We suggest that the albumin corrected anion gap should be calculated to screen for occult tissue anions in these children.

Acid-Base Equilibrium↗

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.

Adolescent↗

Severe upper airway obstruction caused by ulcerative laryngitis.

AIMS: To present our experience of severe upper airway obstruction caused by ulcerative laryngitis in children. METHODS: Retrospective case note review of 263 children with severe upper airway obstruction and a clinical diagnosis of croup admitted to a paediatric intensive care unit (PICU) over a five year period. RESULTS: A total of 148 children (56%) underwent microlaryngoscopy (Storz 3.0 rigid telescope). Laryngeal ulceration with oedema was documented in 15 of these children (10%), median age 14 months (range 10-36) and median weight 10 kg (range 6-12). Twenty seven of the children who underwent microlaryngoscopy (18%) also had ulcerative gingivostomatitis consistent with herpes simplex virus infection. Ulcerative laryngitis was documented in nine of 27 (33%) children with, and in six of 121 (5%) children without, coexistent ulcerative gingivostomatitis. One of the 15 children did not require airway intervention. Nine children required nasotracheal intubation for a median of 4 days (range 3-11) and median PICU stay of 6 days (range 4-14). Five children required tracheostomy ab initio, with a median PICU stay of 30 days (range 20-36), and duration of tracheostomy in situ for a median of 19 days (range 15-253). All 15 children survived. CONCLUSION: Ulcerative laryngitis is more common in our patient population than the few reports suggest. Early diagnostic microlaryngoscopy is recommended in children with severe croup who follow an atypical course.

Airway Obstruction↗

Early hyperlactataemia in critically ill children.

OBJECTIVE: To examine the relationships between early hyperlactataemia, acidosis, organ failure, and mortality in children admitted to intensive care. DESIGN: Prospective observational study. Children with lactate levels > 2 mmol/l were eligible for enrolment. Post-operative patients and those with inherited metabolic disease were excluded. Seven hundred and five children admitted to intensive care were screened, and 50 children with hyperlactataemia (incidence 7%), aged 20.3 months (0.1-191) were enrolled and followed up. The Paediatric Risk of Mortality (PRISM) score, Multiorgan System Failure (MOSF) score, length of ICU stay, and outcome were recorded. Data were collected for lactate (mmol/l), pH, and base excess (BE) until 24 h after admission. Data are reported as median (range) and were analysed by the Mann-Whitney, Fisher's Exact, and Kruskal-Wallis tests, and chisquared test for trend. RESULTS: Overall mortality in the screening group was 70/705 (10%). In the study group (n = 50) median PRISM score was 19 (4-49), median MOSF score 2 (1-4), and observed mortality 32/50 (64%). Median duration of ICU stay was 6 days (2-32) in survivors, and median time until death 3 days (0-13) in nonsurvivors. Eleven nonsurvivors (34%) died within 24 h. In the screening group, hyperlactataemia on admission identified mortality with likelihood ratio = 15. In the study group, neither the admission lactate (3.8 vs 4.6 mmol/l, P = 0.27), pH (7.32 vs 7.30, P = 0.6), nor BE (-7.5 vs -8, P = 0.45) differed significantly between survivors and nonsurvivors. Neither the admission nor peak lactate increased with increasing MOSF score (P = 0.5 and 0.54). The median peak lactate level was 5 mmol/l (2-9.3) in survivors compared to 6.8 mmol/l (2.3-22) in nonsurvivors (P = 0.02), and the cumulative average lactate level was 2.4 mmol/l (1-4.9) in survivors, compared to 4.5 mmol/l (1.6-21) in nonsurvivors (P = 0.0003). Persistent hyperlactataemia 24 h after admission identified mortality with likelihood ratio = 7. CONCLUSION: Hyperlactataemia on admission to intensive care is associated with a high mortality in children. Nonsurvivors within this group may be distinguished by the peak lactate level, or by persistent hyperlactataemia after 24 h of treatment.

Acidosis, Lactic↗

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.

Analysis of Variance↗

Procalcitonin may help differentiate disseminated herpes simplex viral infection from bacterial sepsis in neonates.

UNLABELLED: Disseminated herpes simplex virus infection is a potentially fatal condition which may be difficult to differentiate from bacterial sepsis. We report the case of a neonate with overwhelming herpes simplex (type 2) viraemia who presented with 'septic shock'. CONCLUSION: A low procalcitonin level (1.6 ng/ml), inconsistent with bacteraemia, suggests an alternative aetiology and may strengthen the case for antiviral therapy.

Biomarkers↗

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.

Adolescent↗