Maternal methadone use in pregnancy : factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources

The objectives of this study were to investigate factors associated with the development of neonatal abstinence syndrome (NAS) and to assess the implications for healthcare resources of infants born to drug-misusing women. Design. Retrospective cohort study from 1 January 2004 to 31 December 2006. Setting. Inner-city maternity hospital providing dedicated multidisciplinary care to drug-misusing women. Four hundred and fifty singleton pregnancies of drugmisusing women prescribed substitute methadone in pregnancy. Development of NAS and duration of infant hospital stay. 45.5% of infants developed NAS requiring pharmacological treatment. The odds ratio of the infant developing NAS was independently related to prescribed maternal methadone dose rather than associated polydrug misuse. Breastfeeding was associated with reduced odds of requiring treatment for NAS (OR 0.55, 95% CI 0.34-0.88). Preterm birth did not influence the odds of the infant receiving treatment for NAS. 48.4% infants were admitted to the neonatal unit (NNU) 40% of these primarily for treatment of NAS. The median total hospital stay for all infants was 10 days (interquartile range 7-17 days). Infants born to methadone-prescribed drug-misusing mothers represented 2.9% of hospital births, but used 18.2% of NNU cot days. Higher maternal methadone dose is associated with a higher incidence of NAS. Pregnant drug-misusing women should be encouraged and supported to breastfeed. Their infants are extremely vulnerable and draw heavily on healthcare resources

Incidence and outcome of encapsulating peritoneal sclerosis

Background: Studies report variation in the incidence and outcomes of encapsulating peritoneal sclerosis (EPS). This study reports the incidence and outcome of EPS cases in a national cohort of peritoneal dialysis (PD) patients. Methods: The incident cohort of adult patients who started PD between 1 January 2000 and 31 December 2007 in Scotland (n = 1238) was identified from the Scottish Renal Registry. All renal units in Scotland identified potential EPS cases diagnosed from 1 January 2000 to 31 December 2014, by which point all patients had a minimum of 7 years follow-up from start of PD. Results: By 31 December 2014, 35 EPS cases were diagnosed in the 1238 patient cohort: an overall incidence of 2.8%. The incidence for subgroups with longer PD duration rises exponentially: 1.1% by 1 year, 3.4% by 3 years, 8.8% at 4 years, 9.4% at 5 years and 22.2% by 7 years. Outcomes are poor with mortality of 57.1% by 1 year after diagnosis. Survival analysis demonstrates an initial above-average survival in patients who later develop EPS, which plummets to well below average after EPS diagnosis. Conclusions: The incidence of EPS is reassuringly low provided PD exposure is not prolonged and this supports ongoing use of PD. However, continuing PD beyond 3 years results in an exponential rise in the risk of developing EPS and deciding whether this risk is acceptable should be made on an individual patient basis

A study of dramatic tragedy in the twentieth century

Aristotle, in The Poetic, defines dramatic tragedy as “imitation of a worthy or illustrious and perfect action, possessing magnitude, in pleasing language, using separately the several species of imitation in its parts, by men acting, and not through narration, through pity and fear effecting a purification from such like passions”

Commentary on Gibson et al. (2017): Gestational age and the severity of neonatal abstinence syndrome

No abstract available

Venous needle dislodgement: how to minimize the risks

Although haemodialysis (HD) has become a routine treatment, adverse side effects, and occasionally life threatening clinical complications, still happen. Venous needle dislodgment (VND) is one of the most serious accidents that can occur during HD. If the blood pump is not stopped, either by activation of the protective system of the dialysis machine or manually, the patient can bleed to death within minutes. Fatal and near-fatal blood loss due to VND have been described in the literature (ECRI 1998; Sandroni 2005; Mactier & Worth 2007), but published reports represent only the tip of the ice berg, as such incidents are normally handled at a local or national level. The European Dialysis and Transplant Nurses Association/European Renal Care Association (EDTNA/ERCA) has produced 12 practice recommendations to help reduce the risk of VND and detect blood leakage as early as possible. A poster summarising these recommendations has been created (Van Waeleghem et al. 2008)

Variations in Infant CYP2B6 Genotype Associated with the Need for Pharmacological Treatment for Neonatal Abstinence Syndrome in Infants of Methadone-Maintained Opioid-Dependent Mothers.

Background Neonatal abstinence syndrome (NAS) in infants of methadone-maintained opioid-dependent (MMOD) mothers cannot be predicted in individual cases. We investigated whether variation in infant genotype is associated with severity of NAS. Methods This is a pilot observational cohort study of 21 MMOD mothers and their newborns. Infant buccal swabs were obtained soon after delivery, together with a maternal blood sample for the determination of maternal plasma methadone concentration. Genomic variation in five opioid-related genes (ABCB1, COMT, CYP2B6, CYP2D6, and OPRM1) was ascertained from infant buccal swabs and related to need for pharmacological treatment of NAS. Results Out of 21 infants, 11 (52%) required treatment for NAS. Mothers of treated infants tended to have been prescribed higher doses of methadone, but plasma methadone concentrations did not differ between mothers of treated or untreated babies. Treated and untreated babies did not differ in terms of method of feeding. Treated infants were more likely to carry the normal (homozygous) allele at 516 and 785 regions of CYP2B6 gene (p = 0.015 and 0.023, respectively). There were no differences in any other genes between infants who did or did not require treatment for NAS. Conclusion Genomic variation in CYP2B6 may explain, at least in part, severity of NAS

The electroretinogram and vitamin A in preterm infants

The electroretinogram (ERG) records an electrical potential arising from cells within the retina in response to stimulation by light. As an objective measure of retinal function, electroretinography has potential clinical application in neonates. However, technical difficulties inherent in recording low amplitude responses from unco-operative subjects have limited work in this field, and to date little is known about the normal development of the ERG during the early weeks of life. Plasma concentrations of retinol in the majority of preterm infants are marginal or deficient by adult standards, and there is indirect evidence that this reflects depleted liver stores of vitamin A. At present the functional significance of these observations is unclear. The earliest sign of vitamin A deficiency in adults and older children is impaired dark adaptation, and this is associated with changes in the ERG prior to the onset of subjective nightblindness. Thus, it was anticipated that the development of a reliable method for recording the ERG in the neonatal period might help to determine vitamin A requirements in preterm infants. A technique is described by which the ERG could be studied soon after birth in extremely low birthweight infants. The success rate in recording an interpretable averaged ERG was 96% in term infants and 92% in preterm infants. Results with this method in adult controls were comparable to results obtained by standard techniques. Continuous observation of the infant and assessment of the degree of eye opening was achieved by video monitoring. Minimal restraint was necessary, and no major incidents or complications were encountered. Electroretinograms were recorded successfully in 50 term infants aged between 7 and 148 hours. The amplitude of the ERG was less and the a- and b-wave latencies were longer than in adult controls. Eyelid closure during recording of the ERG significantly increased the a-wave latency and diminished the amplitude of the response. Both the a- and b-wave latencies shortened with advancing postnatal age. Fifty-nine preterm infants were studied at ages ranging from 7 hours to 87 days. The amplitude of the ERG was less and the a-wave latency was longer than in term infants of comparable postnatal age. The ERG was absent initially in two of the most immature infants although each subsequently demonstrated a clearly defined response. Eyelid closure did not have a significant effect upon any of the ERG parameters in preterm infants. The b-wave latency decreased after 48 hours' exposure to light (p < 0. 01) and subsequently was related inversely to postconceptional age. Longitudinal and cross-sectional observations both showed a reduction in the a-and b-wave latencies and an increase in the amplitude of the ERG over time. Maturation of the ERG in preterm infants appears to be mediated, at least in part, by exposure to light. The preterm infants had significantly lower plasma levels of retinol, retinol-binding protein, prealbumin and a-tocopherol than term infants of comparable postnatal age. Plasma concentrations of retinol were below accepted normal levels for older children in all but three preterm infants, and did not change over time. The rise in plasma retinol concentration following an oral dose of 5000 IU retinol (the retinol dose response) suggested that low circulating levels of retinol in preterm infants reflect reduced hepatic reserves of vitamin A. Tocopherol levels were adequate in the majority of preterm infants after the fifth day of life and were higher in infants of all gestational ages fed with own mother's milk. Standard oral vitamin supplementation did not affect plasma levels of either retinol or alpha-tocopherol. A relationship was not demonstrated between any of the averaged ERG parameters and either the plasma concentration of retinol or the retinol dose response. The electroretinographic threshold was measured in 12 preterm infants. Allowing for eye opening, there was a significant reduction in the threshold over time. The logarithm of the electroretinographic threshold correlated with the retinol dose response, but was not related significantly to the predose plasma concentration of retinol. This work suggests that retinal stores of vitamin A in apparently healthy preterm infants are reduced in conjunction with depletion of hepatic reserves. Current recommendations for vitamin A supplementation of preterm infants may be inadequate and require review subsequent to further studies of vitamin A tissue function

The role of lymphatic absorption in peritoneal dialysis

Studies of peritoneal dialysis kinetics have focused on fluid and solute exchange between the peritoneal microcirculation and the hypertonic dialysis solution instilled into the peritoneal cavity. The intraperitoneal fluid, however, is also absorbed continuously by convective flow into the peritoneal cavity lymphatics. Thus, measured net ultrafiltration at the end of each exchange (drain volume minus infusion volume) represents the difference between total net transcapillary fluid transport into and lymphatic drainage out of the peritoneal cavity during the dwell time. Lymphatic absorption from the peritoneal cavity occurs mainly via stomata on the undersurface of the diaphragm and exceeds 50 ml/hour in patients with ascites unless the subdiaphragmatic or mediastinal lymphatics are obstructed by tumour or fibrosis. Lymphatic absorption in the iatrogenic "ascites" of peritoneal dialysis may also be significant and thus merits investigation. The role of lymphatic absorption during peritoneal dialysis was evaluated in a rat model and in adults and children on continuous ambulatory peritoneal dialysis (CAPD). Lymphatic absorption was calculated from the rate of removal of albumin added to the infused dialysis solution, and net transcapillary ultrafiltration was estimated from the dilution of the initial dialysate albumin concentration. Intraperitoneal volume and lymphatic absorption were determined serially during six hour exchanges in rats using 15% dextrose dialysis solution. The net transcapillary ultrafiltration rate decreased exponentially to zero after 330 minutes, whereas lymphatic absorption proceeded at an almost linear rate throughout the exchanges, averaging 4.7 +/- 0.9 (SEM) ml/hour. Peak ultrafiltration volume was observed before osmolar equilibrium between serum and dialysate was reached and occurred when the net transcapillary ultrafiltration rate had decreased to equal the lymphatic absorption rate. Thereafter, the net fluid absorption rate represented lymphatic absorption in excess of concurrent net transcapillary ultrafiltration. Measured net ultrafiltration at the end of the exchanges averaged 24 +/- 2 ml and represented only 46 +/- 5% of total net transcapillary ultrafiltration during the dwell time. Standardised four hour exchanges using 2 litres of 2.5% dextrose dialysis solution were performed in 18 adult CAPD patients. Cumulative lymphatic absorption averaged 343 +/- 39 ml and reduced potential net ultrafiltration at the end of the exchanges by 56 +/- 6%. Extrapolated to four x six hour exchanges per day, lymphatic absorption reduced potential daily net ultrafiltration by 82 +/- 9%, daily drain volumes by 18 +/- 2%, daily urea clearances by 14 +/- 1% and daily creatinine clearances by 13 +/- 1%. These findings indicate that net ultrafiltration and solute clearances are reduced significantly by lymphatic absorption in all CAPD patients. Eight of the patients had transperitoneal solute transport rates indicative of high peritoneal permeability x area. Absolute lymphatic absorption did not differ between patients with average and high peritoneal permeability x area, but caused a proportionately greater reduction in net ultrafiltration in patients with high peritoneal permeability x area (p < 0. 005) since these patients had more rapid glucose absorption from the dialysate (p < 0.001) and lower cumulative net transcapillary ultrafiltration (p < 0.05). Patients with high peritoneal permeability x area had daily net fluid absorption from the dialysis solution even though daily net transcapillary ultrafiltration averaged 2.1 +/- 0.4 litres. Failure of peritoneal ultrafiltration in CAPD, in the absence of a dialysate leak, occurs when daily lymphatic absorption exceeds daily net transcapillary ultrafiltration. Four hour exchanges using 40 ml/Kg of 2.5% dextrose dialysis solution were performed in six children on peritoneal dialysis. Cumulative lymphatic absorption averaged 10.4 +/- 1.6 ml/Kg and reduced total net transcapillary ultrafiltration by 73 +/- 10%. Extrapolated to four x six hour exchanges per day, lymphatic absorption reduced potential daily drain volumes by 27 +/- 5%, daily urea clearances by 24 +/- 4% and daily creatinine clearances by 22 +/-5%. The infusion volumes of dialysis solution, corrected for body surface area, were similar in children and adults. Net ultra- filtration, scaled for body surface area, was lower in children than in adults with average peritoneal permeability x area (p < 0.05) due to a combination of relatively higher lymphatic absorption and lower net transcapillary ultrafiltration. Thus, lymphatic absorption caused a proportionately greater reduction in net ultrafiltration and solute clearances in children than in adults. These studies emphasise the important contribution of lymphatic absorption to loss of ultrafiltration and solute clearances after long-dwell peritoneal dialysis exchanges. Thus, reappraisal of current understanding of peritoneal dialysis kinetics is required to incorporate the role of lymphatics. Pharmacological reduction of lymphatic absorption may provide an alternative means of improving the efficiency of peritoneal dialysis without altering transperitoneal transport of water and solutes into the peritoneal cavity