A Durward

Guy's and St Thomas' NHS Foundation Trust, Londinium, England, United Kingdom

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Publications (78)352.97 Total impact

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    ABSTRACT: Objectives Once-daily gentamicin therapy is becoming increasingly common in paediatric practice; however, little is known about pharmacokinetics in critical illness. Gentamicin exhibits concentration dependent killing; thus, peak serum concentrations at least eight times higher than minimum inhibition concentration of the target organism have been recommended. We wanted to derive pharmacokinetic parameters for gentamicin in critical illness and to evaluate whether a dose of 8 mg/kg provides an adequate peak serum concentration (>16 mg/l).Methods Population-based pharmacokinetic analyses were undertaken using therapeutic drug monitoring data collected prospectively in an intensive care unit over 6 months (n=50 children). Monte Carlo simulations were used to estimate the probability of achieving (1) peak concentrations >16 mg/l; and (2) trough concentrations 16 mg/l in critically ill children. A considerable proportion will require dose intervals >24 h; thus, therapeutic drug monitoring is essential.
    Archives of Disease in Childhood 01/2010; 95(6). · 2.91 Impact Factor
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    Neuromuscular Disorders 09/2009; 19(8):588-589. · 3.13 Impact Factor
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    ABSTRACT: Once-daily gentamicin therapy is becoming increasingly common in pediatric practice; however, little is known about pharmacokinetics in critical illness. Gentamicin exhibits concentration dependant killing; thus, peak serum concentrations at least eight times higher than minimum inhibition concentration of the target organism have been recommended. We wanted to derive pharmacokinetic parameters for gentamicin in critical illness and to evaluate whether a dose of 8 mg/kg provides an adequate peak serum concentration (>16 mg/L). Population-based pharmacokinetic analyses were undertaken using therapeutic drug monitoring data collected prospectively in an intensive care unit over 6 months (n = 50 children). Monte Carlo simulations were used to estimate the probability of achieving 1) peak concentrations >16 mg/L; and 2) trough concentrations <2 mg/L at 24 and 36 hrs. The optimal pharmacokinetic model was of two-compartment disposition with zero order input and additive residual error. Weight was associated nonlinearly with clearance and linearly with volume, and age was a significant covariate for clearance. An 8-mg/kg dose provided near 100% probability of achieving adequate peak concentrations at all ages. However this probability decreased rapidly at doses <7 mg/kg with neonates being the most susceptible. Approximately 50% of nonpremature neonates within the first week of life, 25% of infants, and 10% of children are likely to need a dose interval >24 hrs. A gentamicin dose of 8 mg/kg is highly likely to achieve peak concentrations >16 mg/L in critically ill children. A considerable proportion will require dose intervals >24 hrs; thus, therapeutic drug monitoring is essential.
    Pediatric Critical Care Medicine 09/2009; 11(2):267-74. · 2.33 Impact Factor
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    ABSTRACT: To report the first case of congenital central hypoventilation syndrome (CCHS) presenting with severe cor pulmonale in an adolescent. Case report and literature review. Our Institutional Review Board waived the need for consent. Pediatric intensive care unit in a tertiary care children's hospital. A 12-year-old girl who developed profound hypoxia following routine dental extraction under intravenous opiate sedation and became progressively obtunded due to marked hypoventilation without hypoxic arousal, requiring mechanical ventilation. She had evidence of severe right heart failure, but no cardiac, pulmonary, neurologic, or neuromuscular cause was identified. The diagnosis of CCHS was suspected and subsequently confirmed by blood polymerase chain reaction analysis that revealed a heterozygous polyalanine expansion mutation of the PHOX2B gene (five polyalanine repeats). This report describes the unusual presentation of severe cor pulmonale in an adolescent with so-called "late-onset" CCHS. CCHS was previously thought to be a disease affecting only neonates, but the late-onset phenotype has now been well described in adults. It should be considered in any child presenting with unexplained right heart failure without an identifiable cause, particularly if central sleep apnea is present, because early initiation of ventilatory support can prevent cardiac and neurologic sequelae and improve outcome.
    Pediatric Critical Care Medicine 08/2009; 10(4):e41-2. · 2.33 Impact Factor
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    Critical Care 01/2009; 13(Suppl 1). · 5.04 Impact Factor
  • Shane M Tibby, Andrew Durward
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    ABSTRACT: Pulmonary artery (PA) banding has been established as a palliative surgical technique for congenital heart defects for over 50 years [1]. With the advent of earlier corrective surgery, the indications for PA banding have changed over time [2, 3]. Currently these include: (a) limitation of pulmonary blood flow in the setting of an excessive left-toright shunt; (b) regulation of pulmonary blood flow in the univentricular circulation; and (c) a training procedure for the left ventricle prior to conversion to the systemic pumping chamber (late presentation of D-transposition of the great arteries, or prior to a double-switch procedure with L-transposition).
    Intensive Care Medicine 02/2008; 34(1):203-7. · 5.54 Impact Factor
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    S Tibby, A Durward
    Critical Care 01/2008; 12. · 5.04 Impact Factor
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    ABSTRACT: Metabolic acidosis is common in septic shock, yet few data exist on its etiological temporal profile during resuscitation; this is partly due to limitations in bedside monitoring tools (base excess, anion gap). Accurate identification of the type of acidosis is vital, as many therapies used in resuscitation can themselves produce metabolic acidosis. Retrospective, cohort study. Multidisciplinary pediatric intensive care unit with 20 beds. A total of 81 children with meningococcal septic shock. None. Acid-base data were collected retrospectively on 81 children with meningococcal septic shock (mortality, 7.4%) for the 48 hrs after presentation to the hospital. Base excess was partitioned using abridged Stewart equations, thereby quantifying the three predominant influences on acid-base balance: sodium chloride, albumin, and unmeasured anions (including lactate). Metabolic acidosis was common at presentation (mean base excess, -9.7 mmol/L) and persisted for 48 hrs. However, the pathophysiology changed dramatically from one of unmeasured anions at admission (mean unmeasured anion base excess, -9.2 mmol/L) to predominant hyperchloremia by 8-12 hrs (mean sodium-chloride base excess, -10.0 mmol/L). Development of hyperchloremic acidosis was associated with the amount of chloride received during intravenous fluid resuscitation (r = .44), with the base excess changing, on average, by -0.4 mmol/L for each millimole per kilogram of chloride administered. Hyperchloremic acidosis resolved faster in patients who 1) manifested larger (more negative) sodium chloride-partitioned base excess, 2) maintained a greater urine output, and 3) received furosemide; and slower in those with high blood concentrations of unmeasured anions (all, p < .05). Hyperchloremic acidosis is common and substantial after resuscitation for meningococcal septic shock. Recognition of this entity may prevent unnecessary and potentially harmful prolonged resuscitation.
    Critical Care Medicine 10/2007; 35(10):2390-4. · 6.15 Impact Factor
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    Critical Care 01/2007; 11. · 5.04 Impact Factor
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    ABSTRACT: To demonstrate the diagnostic yield, therapeutic role and safety of flexible bronchoscopy via an intensivist-led service in critically ill children. Retrospective chart review. Regional paediatric intensive care unit. One hundred forty-eight flexible bronchoscopies were performed by two intensivists on 134 patients (median age 16.5 months) over a 2.5-year period. Eighty-eight percent of patients required mechanical ventilation, and 22% were receiving inotropes. Case mix included general (n = 77), cardiac surgery (n = 18), cardiology (n = 13), ear-nose-and-throat surgery (n = 17), oncology (n = 8) and renal (n = 1). The indication for bronchoscopy was defined a priori according to one of four categories: suspected upper airway disease (n = 32); lower airway disease (n = 70); investigation of pulmonary disease (n = 25); and extubation failure (n = 21). Bronchoscopy was generally performed soon after PICU admission, at a median time of 1.5 days for the former three categories, and 4 days for extubation failure group. A positive yield from bronchoscopy (diagnosis that explained the clinical condition or influenced patient management) was present in 113 of 148 (76%) procedures, varying within groups from 44% (pulmonary disease) to 90% (extubation failure). Ten percent of patients developed a fall in oxygen saturations > 20% during the procedure and 17% required a bolus of at least 10 ml/kg of 0.9% saline for hypotension. Critically ill patients with respiratory problems may benefit from a PICU-led bronchoscopy service as the yield for positive bronchoscopic finding is high, particularly for upper airway problems or extubation failure.
    Intensive Care Medicine 01/2007; 32(12):2026-33. · 5.54 Impact Factor
  • Shane Tibby, Andrew Durward
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    ABSTRACT: Without Abstract
    Intensive Care Medicine 09/2006; 32(9):1445-1445. · 5.54 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Pediatric Critical Care Medicine 06/2006; 7(4):409. · 2.33 Impact Factor
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    ABSTRACT: During the acute treatment of diabetic ketoacidosis we (a) determined the temporal incidence of hyperchloraemia, and (b) quantified the influence of hyperchloraemia on interpretation of common blood gas derived acid base parameters, namely base deficit and bicarbonate. Retrospective chart review in two regional paediatric intensive care units. Stewart's physicochemical theory was used to develop regression equations quantifying the acidifying effect of hyperchloraemia on both base deficit and bicarbonate. These were then applied retrospectively to blood chemistry results from 18 children (median age 12.7 years, weight 43 kg) with diabetic ketoacidosis. Plasma ketonaemia was estimated using the albumin-corrected anion gap. The incidence of hyperchloraemia, as documented by a ratio of plasma chloride to sodium of greater than 0.79, increased from 6% at admission to 94% after 20 h of treatment. Correction for chloride produced a dramatic improvement in the relationship between changes in the anion gap vs. both base deficit (from R(2)=0.55 to R(2)=0.95) and bicarbonate (from R(2)=0.51 to R(2)=0.96) during treatment. After 20 h of treatment the mean base deficit had decreased from 24.7 mmol/l to 10.0 mmol/l however, the proportion that was due to hyperchloraemia increased from 2% to 98%. It is now possible using a simple correction factor to quantify the confounding effect of hyperchloraemia on both base deficit and bicarbonate in diabetic ketoacidosis. This bedside tool may be a useful adjunct to guide therapeutic interventions.
    Intensive Care Medicine 03/2006; 32(2):295-301. · 5.54 Impact Factor
  • Andrew Durward
    Pediatric Critical Care Medicine 02/2006; 7(1):93-4; author reply 94-7. · 2.33 Impact Factor
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    Critical Care 01/2006; 10. · 5.04 Impact Factor
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    Critical Care 01/2006; 10. · 5.04 Impact Factor
  • Andrew Durward
    Pediatric Critical Care Medicine 01/2006; 7(1):93-94. · 2.33 Impact Factor
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    A Durward, D Taylor, S Tibby, I Murdoch
    Critical Care 01/2006; 10. · 5.04 Impact Factor
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    ABSTRACT: The base deficit is a useful tool for quantifying total acid-base derangement, but cannot differentiate between various aetiologies. The Stewart-Fencl equations for strong ions and albumin have recently been abbreviated; we hypothesised that the abbreviated equations could be applied to the base deficit, thus partitioning this parameter into three components (the residual being the contribution from unmeasured anions). The two abbreviated equations were applied retrospectively to blood gas and chemistry results in 374 samples from a cohort of 60 children with meningococcal septic shock (mean pH 7.31, mean base deficit -7.4 meq/L). Partitioning required the simultaneous measurement of plasma sodium, chloride, albumin and blood gas analysis. After partitioning for the effect of chloride and albumin, the residual base deficit was closely associated with unmeasured anions derived from the full Stewart-Fencl equations (r2 = 0.83, y = 1.99 - 0.87x, standard error of the estimate = 2.29 meq/L). Hypoalbuminaemia was a common finding; partitioning revealed that this produced a relatively consistent alkalinising effect on the base deficit (effect +2.9 +/- 2.2 meq/L (mean +/- SD)). The chloride effect was variable, producing both acidification and alkalinisation in approximately equal proportions (50% and 43%, respectively); furthermore the magnitude of this effect was substantial in some patients (SD +/- 5.0 meq/L). It is now possible to partition the base deficit at the bedside with enough accuracy to permit clinical use. This provides valuable information on the aetiology of acid-base disturbance when applied to a cohort of children with meningococcal sepsis.
    Critical care (London, England) 09/2005; 9(4):R464-70. · 5.04 Impact Factor
  • Andrew Durward, Shane M Tibby
    Journal of Pediatrics 09/2005; 147(2):273; author reply 274-5. · 3.74 Impact Factor

Publication Stats

769 Citations
352.97 Total Impact Points

Institutions

  • 2005–2013
    • Guy's and St Thomas' NHS Foundation Trust
      • Paediatric Intensive Care Unit (PICU)
      Londinium, England, United Kingdom
  • 2012
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      • Paediatric Intensive Care Unit (PICU)
      Newcastle-on-Tyne, England, United Kingdom
  • 2011
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 2004
    • Alder Hey Children's Healthcare Hospital
      Liverpool, England, United Kingdom
  • 2000–2003
    • SickKids
      • • Unit of Critical Care
      • • Department of Critical Care Medicine
      Toronto, Ontario, Canada
  • 2002
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom