Fetal effects of combined spinal‐epidural vs epidural labour analgesia: a prospective,randomised double‐blind study

We have compared fetal heart rate patterns, Apgar scores and umbilical cord gas values following initiation of labour analgesia using either combined spinal‐epidural or epidural. One hundred and fifteen healthy women requesting neuraxial analgesia in the first stage of labour were randomly assigned to receive either combined spinal‐epidural (n = 62) or epidural analgesia (n = 53). Fetal heart rate traces, recorded for 30 min before and 60 min after neuraxial block, were categorised as normal, suspicious or pathological according to national guidelines. Sixty‐one fetal heart rate tracings were analysed in the combined spinal‐epidural group and 52 in the epidural group. No significant differences were found in fetal heart rate patterns, Apgar scores or umbilical artery and vein acid‐base status between groups. However, in both combined spinal‐epidural and epidural groups, there was a significant increase in the incidence of abnormal fetal heart rate patterns following neuraxial analgesia (p < 0.0001); two before compared with eight after analgesia in the combined spinal‐epidural group and zero before compared with 11 after in the epidural group. These changes comprised increased decelerations (p = 0.0045) (combined spinal‐epidural group nine before and 14 after analgesia, epidural group four before and 16 after), increased late decelerations (p < 0.0001) (combined spinal‐epidural group zero before and seven after analgesia, epidural group zero before and eight after), and a reduction in acceleration rate (p = 0.034) (combined spinal‐epidural group mean (SD) 12.2 (6.7) h^?1 before and 9.9 (6.1) h^?1 after analgesia, epidural group 11.0 (7.3)  h^?1 before and 8.4 (5.9) h^?1 after). These fetal heart rate changes did not affect neonatal outcome in this healthy population.     

Effects of magnesium sulphate on coagulation after laparoscopic colorectal cancer surgery,measured by rotational thromboelastometry (ROTEM®)

We investigated the effects of magnesium sulphate on blood coagulation profiles using rotational thromboelastometry in patients undergoing laparoscopic colorectal cancer surgery. Patients were randomly allocated to the magnesium group (n = 22) or control group (n = 22). The magnesium group received intravenous magnesium sulphate (50 mg.kg^?1 followed by a continuous infusion of 15 mg.kg^?1.h^?1), whereas the control group received the same volume of isotonic saline. Mean (SD) postoperative serum magnesium levels were 1.60 (0.13) mmol.l^?1 in the magnesium group compared with 0.98 (0.06) mmol.l^?1 in the control group (p < 0.001). All maximum clot firmness values of ROTEM analysis were significantly lower on the third postoperative day in the magnesium group compared with the control group (p < 0.05). We conclude that ROTEM analysis demonstrated that intra‐operative administration of intravenous magnesium sulphate reduces blood hypercoagulability in patients undergoing laparoscopic colorectal cancer surgery.     

Remifentanil for labour analgesia: a double‐blinded,randomised controlled trial of maternal and neonatal effects of patient‐controlled analgesia versus continuous infusion

This trial aimed to compare the maternal and neonatal effects of remifentanil given by patient‐controlled analgesia (PCA) or continuous infusion for labour analgesia. Patient controlled analgesia was administered using increasing stepwise boluses from 0.1 to 0.4 μg.kg^?1 (0.1 μg.kg^?1 increment, 2 min lockout, n = 30). Continuous infusion used rates from 0.05 to 0.2 μg.kg^?1.min^?1 (0.05 μg.kg^?1.min^?1 increment, n = 30). Dose increments were given on request. Women reported lowest pain scores (median (IQR [range]) of 3 (2–4 [2–5]) for PCA and 4 (3–5.25 [3–7]) for continuous infusion (p = 0.004) at 60 min after the beginning of analgesia. The mean (SD) remifentanil umbilical vein/maternal artery ratio in the PCA and infusion groups were 0.74 (0.45) vs 0.70 (0.52), respectively (p = 0.776). The mean (SD) umbilical artery/umbilical vein ratios were 0.31 (0.12) vs 0.26 (0.07), respectively (p = 0.088). Maternal and neonatal adverse reactions of remifentanil were similar between the two groups. The total remifentanil consumption (median (IQR [range]) during PCA administration was lower than continuous infusion, 1.34 (1.22–1.48 [0.89–1.69]) mg vs 1.49 (1.35–1.61 [1.12–1.70] mg; p = 0.011). The results suggest that remifentanil PCA provides better pain relief and similar placental transfer compared with continuous infusion.     

The effects of intra‐operative dexmedetomidine on postoperative pain,side‐effects and recovery in colorectal surgery

In this double‐blind, randomised study, 100 patients undergoing open or conventional laparoscopic colorectal surgery received an intra‐operative loading dose of dexmedetomidine 1 μg.kg^?1 followed by an infusion of 0.5 μg.kg^?1.h^?1, or a bolus and infusion of saline 0.9% of equivalent volume. Forty‐six patients in the dexmedetomidine group and 50 in the saline group completed the study. The area under the curve of numerical rating scores for pain at rest for 1–48 h postoperatively was significantly lower in the patients receiving dexmedetomidine (p = 0.041). There was no difference in morphine consumption, duration of recovery ward or hospital stay. From the data obtained in this study, we calculated a number needed to treat for effective pain relief of 4. Intra‐operative dexmedetomidine in colorectal surgery resulted in a reduction in resting pain scores, but there was no morphine‐sparing effect or improvement in patients' recovery outcome measures.     

Validation of long‐term survival prediction for scheduled abdominal aortic aneurysm repair with an independent calculator using only pre‐operative variables

We observed survival after scheduled repair of abdominal aortic aneurysm in 1096 patients for a median (IQR [range]) of 3.0 (1.5–5.8 [0–15]) years: 943 patients had complete data, 250 of whom died. We compared discrimination and calibration of an external model with the Kaplan–Meier model generated from the study data. Integrated Brier misclassification scores for both models at 1–5 postoperative years were 0.04, 0.08, 0.11, 0.13 and 0.16, respectively. Harrel's concordance index at 1–5 postoperative years was 0.73, 0.71, 0.68, 0.67 and 0.66, respectively. Groups with median 5‐year predicted mortality of 40% (n = 251), 18% (n = 414) and 8% (n = 164) had lower observed mortality than 114 patients with 70% predicted mortality, hazard ratio (95% CI): 0.58 (0.37–0.76), p = 0.0031; 0.30 (0.19–0.48), p = 1.7 × 10^?12 and 0.19 (0.13–0.27), p = 1.3 × 10^?10, respectively, test for trend p = 5.6 × 10^?15. Survival predicted by the external calculator was similar to the Kaplan–Meier estimate.     

A comparison of the i‐gel™ and the PRO‐Breathe® laryngeal mask during pressure support ventilation in children

Many studies comparing the i‐gel^? with laryngeal masks include patients in whom laryngeal mask cuff inflation pressures are higher than recommended, or involve the use of neuromuscular blocking drugs and positive pressure ventilation. We compared the i‐gel with the PRO‐Breathe^® laryngeal mask in anaesthetised, spontaneously breathing children. Two hundred patients aged up to 16 years were randomly allocated to either the i‐gel or the PRO‐Breathe laryngeal mask. The PRO‐Breathe was inflated to an intracuff pressure of 40 cmH₂O. All patients received pressure support of 10 cmH₂O and positive end‐expiratory pressure of 5 cmH₂O. Successful insertion at the first attempt was 82% for the i‐gel compared with 93% for the PRO‐Breathe (p = 0.019). Leakage volume was significantly higher with i‐gel sizes 1.5 (p = 0.015), 2 (p = 0.375), 2.5 (p = 0.021) and 3 (p = 0.003) compared with the equivalent‐sized PRO‐Breathe device. Device dislodgement following successful initial placement was more frequent with the i‐gel (5%) compared with the PRO‐Breathe laryngeal mask (0%). We conclude that the PRO‐Breathe laryngeal mask is superior to the i‐gel in terms of leakage volume and device dislodgement.     

The intubation scoop (i‐scoop) – a new type of laryngoscope for difficult and normal airways

The i‐scoop is an intubation device with a curved guiding bar with laterally located lenses at its tip, rather than a blade. Twenty‐five anaesthesiologists intubated a manikin that simulated first a normal and then a difficult airway. All participants were able to intubate the difficult airway with a good view of the glottis using the i‐scoop. None was able to intubate using seven other laryngoscopes (Macintosh laryngoscope, GlideScope^® GVL and AVL, McGrath^® (Series 5/MAC), C‐MAC^®, A.P. Advance^?). Intubation was successful only with the Airtraq^® (n = 10), the Airway Scope (n = 5), the C‐MAC D‐Blade (n = 2), the A.P. Advance DAB (n = 1) and the GlideScope DL Trainer (n = 1) (p < 0.001, success rate of i‐scoop vs all 12 laryngoscopes combined). In contrast to all other videolaryngoscopes, intubation of the normal airway with the i‐scoop was achieved even faster than with the Macintosh laryngoscope (p < 0.02). The i‐scoop outperformed all other laryngoscopes in both difficult and normal airways, and therefore has potential as an easier and safer alternative to present devices.     

A prospective randomised comparison of two insertion methods for i‐gel™ placement in anaesthetised paralysed patients: standard vs rotational technique

In this prospective randomised study, we compared two techniques for i‐gel^? insertion. One hundred and eighty‐one anaesthetised, paralysed adult patients were randomly allocated into one of two groups. In the standard group (n = 91), the i‐gel was inserted using the standard technique. In the rotation group (n = 90), the i‐gel was rotated 90° anticlockwise in the mouth and re‐rotated in the hypopharynx to the original alignment. The success rate, insertion time, air leak pressure and complications were assessed. The success rate for insertion at the first attempt was lower for the standard technique, 78 (86%) vs 87 (97%; p = 0.016). The mean (SD) insertion time was longer (26.9 (14.5) s vs 22.4 (10.2) s; p = 0.016) and air leak pressure was lower (22.5 (10.4) cmH₂O vs 27.1 (9.4) cmH₂O; p = 0.002) in the standard group. The incidence of bloodstaining was higher with the standard technique (8 (9%) vs 1 (1%); p = 0.034). This study suggests that the rotational technique is superior to the standard technique for i‐gel insertion.     

Transthoracic echocardiographic assessment of haemodynamics in severe pre‐eclampsia and HIV in South Africa

Haemodynamic and cardiac structural changes in severe pre‐eclampsia and in pregnant women with human immunodeficiency virus (HIV) infection have not been clearly established. We performed transthoracic echocardiography on 105 women. Women with pre‐eclampsia demonstrated (mean (SD), untreated vs treated) preserved fractional shortening (40 (7.1)% vs 41 (8.6)%), a non‐dilated left ventricle (4.5 (0.49) cm vs 4.4 (0.44) cm), increased mitral valve E/septal e′ (10.5 (3.3) vs 10.6 (2.8)), and preserved tricuspid annular plane systolic exertion (2.6 (0.36) cm vs 2.4 (0.51) cm). Women with HIV infection demonstrated (mean (SD), HIV‐positive vs healthy) a reduced cardiac index (2.8 (0.64) ml.min^?1.m^?2 vs 3.1 (0.7) ml.min^?1.m^?2, p = 0.029), reduced septal s′ tissue Doppler velocity (8.5 (1.5) cm.s^?1 vs 9.3 (1.7) cm.s^?1, p = 0.042), increased left ventricular end‐diastolic area (7.6 (2.1) cm² vs 6.3 (1.7) cm²_, p = 0.004), and reduced right ventricular s′ and e′ velocity (s′ velocity 14.7 (3.1) cm.s^?1 vs 7.0 (2.9) cm.s^?1 p = 0.001, e′ velocity 16.3 (4.1) cm.s^?1 vs 18.7 (3.4) cm.s^?1, p = 0.013). The mitral value E/septal e′ was > 8 in 39% of patients with HIV. Fractional shortening (< 28%) was reduced in 10% of healthy women, and mitral valve E/septal e′ ratios were > 8 in 38% of that group. Women with pre‐eclampsia demonstrated preserved systolic function, with diastolic dysfunction. Women with HIV demonstrated reduced left and right ventricular systolic function, with increased ventricular dilatation.     

Pulse pressure variation to predict fluid responsiveness in spontaneously breathing patients: tidal vs forced inspiratory breathing

We evaluated whether pulse pressure variation can predict fluid responsiveness in spontaneously breathing patients. Fifty‐nine elective thoracic surgical patients were studied before induction of general anaesthesia. After volume expansion with hydroxyethyl starch 6 ml.kg^?1, patients were defined as responders by a ≥ 15% increase in the cardiac index. Haemodynamic variables were measured before and after volume expansion and pulse pressure variations were calculated during tidal breathing and during forced inspiratory breathing. Median (IQR [range]) pulse pressure variation during forced inspiratory breathing was significantly higher in responders (n = 29) than in non‐responders (n = 30) before volume expansion (18.2 (IQR 14.7–18.2 [9.3–31.3])% vs 10.1 (IQR 8.3–12.6 [4.8–21.1])%, respectively, p < 0.001). The receiver‐operating characteristic curve revealed that pulse pressure variation during forced inspiratory breathing could predict fluid responsiveness (area under the curve 0.910, p < 0.0001). Pulse pressure variation measured during forced inspiratory breathing can be used to guide fluid management in spontaneously breathing patients.     

Ten‐year outcomes in a randomized phase II study of kidney transplant recipients administered belatacept 4‐weekly or 8‐weekly

In the phase II IM103‐100 study, kidney transplant recipients were first randomized to belatacept more‐intensive‐based (n = 74), belatacept less‐intensive‐based (n = 71), or cyclosporine‐based (n = 73) immunosuppression. At 3‐6 months posttransplant, belatacept‐treated patients were re‐randomized to receive belatacept every 4 weeks (4‐weekly, n = 62) or every 8 weeks (8‐weekly, n = 60). Patients initially randomized to cyclosporine continued to receive cyclosporine‐based immunosuppression. Cumulative rates of biopsy‐proven acute rejection (BPAR) from first randomization to year 10 were 22.8%, 37.0%, and 25.8% for belatacept more‐intensive, belatacept less‐intensive, and cyclosporine, respectively (belatacept more‐intensive vs cyclosporine: hazard ratio [HR] = 0.95; 95% confidence interval [CI] 0.47‐1.92; P = .89; belatacept less‐intensive vs cyclosporine: HR = 1.61; 95% CI 0.85‐3.05; P = .15). Cumulative BPAR rates from second randomization to year 10 for belatacept 4‐weekly, belatacept 8‐weekly, and cyclosporine were 11.1%, 21.9%, and 13.9%, respectively (belatacept 4‐weekly vs cyclosporine: HR = 1.06, 95% CI 0.35‐3.17, P = .92; belatacept 8‐weekly vs cyclosporine: HR = 2.00, 95% CI 0.75‐5.35, P = .17). Renal function trends were estimated using a repeated‐measures model. Estimated mean GFR values at year 10 for belatacept 4‐weekly, belatacept 8‐weekly, and cyclosporine were 67.0, 68.7, and 42.7 mL/min per 1.73 m², respectively (P<.001 for overall treatment effect). Although not statistically significant, rates of BPAR were 2‐fold higher in patients administered belatacept every 8 weeks vs every 4 weeks.     

Conditioning out‐of‐date bank‐stored red blood cells using a cell‐saver auto‐transfusion device: effects on numbers of red cells and quality of suspension fluid

We investigated the utility of a cell‐saver device for processing out‐of‐date red blood cells, by washing twenty bags of red blood cells that had been stored for between 36 and 55 days. The volume of recovered cells, and the characteristics of the suspension fluid, were measured before and after treatment. The ratio of free haemoglobin to total haemoglobin was up to 0.02 before processing, and up to 0.011 afterwards, changing by between ?0.013 and +0.003. This ratio met the current standard for free haemoglobin (less than 0.008 in more than 75% of samples), both before and after processing. Ninety‐three percent of red blood cells survived the process. Potassium ion concentration fell from above 15 mmol.l^?1 in all cases, to a mean of 6.4 mmol.l^?1 (p < 0.001). The pH rose to a mean value of 6.44 (p = 0.001). Lactate ion concentration fell to a mean value of 14 mmol.l^?1 (p < 0.001). Sodium ion concentration rose from a mean value of 93 mmol.l^?1 to a mean value of 140 mmol.l^?1 (p < 0.001). A useful proportion of out‐of‐date red blood cells remained intact after conditioning using a cell‐saver, and the process lowered concentrations of potentially toxic solutes in the fluid in which they were suspended.     

Re‐exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies

Re‐exposure to beta cell autoantigens and its relevance in the presence of donor‐specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty‐three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma‐associated antigen 2 (IA‐2), insulin (micro‐IAA [mIAA]), and islet‐specific zinc transporter isoform‐8 (ZnT8). Twenty‐five (75.7%) had pre‐transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA‐2 n = 2, GA65 + mIAA+IA‐2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA‐2 (>0.16), and ZnT8 (p > 0.07) were observed between pre‐transplant and post‐transplant at 6 or 12 months. A decrease in mIAA from pre‐ to post‐6 months (p < 0.0001), 12 months (p < 0.0001), and from post‐6 to post‐12 months (p = 0.0002) was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow‐up (three yr). Re‐exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.     

The minimally invasive MitraClip™ procedure for mitral regurgitation under general anaesthesia: immediate effects on the pulmonary circulation and right ventricular function

A relatively new minimally invasive cardiological procedure, called the MitraClip^?, does not require sternotomy and may have a number of advantages compared with open mitral valve surgery, but its acute impact on the pulmonary circulation and right ventricular function during general anaesthesia is unclear. We prospectively assessed the effects of the MitraClip procedure in 81 patients with or without pulmonary hypertension (defined as mean pulmonary artery pressure > 25 mmHg), who were anaesthetised using fentanyl (5 μg.kg^?1), etomidate (0.2–0.3 mg.kg^?1), rocuronium (0.5–0.6 mg.kg^?1) and isoflurane. Placement of the MitraClip led to a 60% increase in mean (SD) right ventricular stroke work index (from 512 (321) to 820 (470) mmHg.ml.m^?2, p < 0.0001), while mean (SD) pulmonary vascular resistance index decreased by 24% (522 (330) to 399 (244) dyn.s.cm^?5, p < 0.0001), and mean (SD) pulmonary artery pressure decreased by 10% (30 (8) to 27 (8) mmHg, p < 0.0001). Patients with pulmonary hypertension experienced a similar decrease in mean pulmonary artery pressure compared with those without, and they also had a slight reduction in mean (SD) pulmonary artery occlusion pressure (22 (6) down to 20 (6) mmHg, p = 0.044). We conclude that successful MitraClip treatment for mitral regurgitation acutely improves right ventricular performance by reducing right ventricular afterload, regardless of whether patients have pre‐operative pulmonary hypertension.     

Stylet‐ or forceps‐guided tube exchanger to facilitate GlideScope® intubation in simulated difficult intubations – a randomised controlled trial

The GlideScope^® videolaryngoscope is widely used in the management of the difficult airway. However, passing the tracheal tube through the vocal cords can be awkward, and the use of a stylet to guide insertion is recommended. This randomised controlled trial evaluated a forceps‐guided tube exchanger as an alternative to the stylet to aid intubation with the GlideScope in patients undergoing anaesthesia, with a simulated difficult airway created by the application of a semi‐rigid cervical collar. Data were analysed from 178 patients randomly assigned to undergo intubation using either the stylet (n = 88) or a forceps‐guided tube exchanger (n = 90). All intubations were completed successfully, with first attempt rates of 93.2% using the stylet and 94.4% using the exchanger (p = 0.597). The mean (SD) intubation time was 67.8 (28.7) s in the stylet group and 66.1 (15.5) s in the forceps‐guided tube exchanger group (p = 0.11). The frequency of sore throat 1 h after extubation was 34.1% in the stylet group and 2.2% in the tube exchanger group (p < 0.001); 24 h after extubation the corresponding figures were 40.0% and 11.1% (p < 0.001). Using a forceps‐guided tube exchanger may offer an advantage over a stylet in guiding tracheal intubation when the GlideScope is used.     

A randomised comparison of variable‐frequency automated mandatory boluses with a basal infusion for patient‐controlled epidural analgesia during labour and delivery

This trial was conducted to compare the analgesic efficacy of administering variable‐frequency automated boluses at a rate proportional to the patient's needs with fixed continuous basal infusion in patient‐controlled epidural analgesia (PCEA) during labour and delivery. We recruited a total of 102 parturients in labour who were randomly assigned to receive either a novel PCEA with automated mandatory boluses of 5 ml administered once, twice, three or four times per hour depending on the history of the parturient's analgesic demands over the past hour (Automated bolus group), or a conventional PCEA with a basal infusion of 5 ml.h^?1 (Infusion group). The incidence of breakthrough pain requiring supplementation by an anaesthetist was significantly lower in the Automated bolus group, three out of 51 (5.9%) compared with the Infusion group, 12 out of 51 (23.5%, p = 0.023). The time‐weighted mean (SD) hourly consumption of ropivacaine was similar in both groups, 10.0 (3.0) mg in the Automated bolus group vs 11.1 (3.2) mg in the Infusion group (p = 0.06). Parturients from the Automated bolus group reported higher satisfaction scores compared with those in the Infusion group, 96.5 (5.0) vs 89.2 (9.4), respectively (p < 0.001). There was no difference in the incidence of maternal side‐effects and obstetric and neonatal outcomes.     

The effect of magnesium sulphate infusion on the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia

This randomised, controlled, double‐blind study investigated the effects of intra‐operative magnesium sulphate administration on the incidence of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia. Seventy children were randomly allocated to receive a 30 mg.kg^?1 bolus of intravenous magnesium sulphate after induction of anaesthesia followed by a continuous infusion of 10 mg.kg^?1.h^?1 or an equal volume of saline 0.9%. All children received titrated sevoflurane anaesthesia adjusted to maintain haemodynamic stability. The Pediatric Anesthesia Emergence Delirium scale and the Children's Hospital of Eastern Ontario Score were used for the assessment of postoperative emergence agitation and pain, respectively. Emergence agitation was more common in the control group than in the magnesium group (23 (72%) and 12 (36%), respectively (p = 0.004)), with a relative risk of 0.51 (95% CI 0.31–0.84), an absolute risk reduction of 0.35 (95% CI 0.10–0.54), and number needed to treat of 3 (95% CI 2–9). Postoperative pain scores were comparable in the two groups. Magnesium sulphate reduces the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia and is not associated with increased postoperative side‐effects or delayed recovery.     

Dexmedetomidine pharmacokinetics in pediatric intensive care – a pooled analysis

Background: Published dexmedetomidine pharmacokinetic studies in children are limited by participant numbers and restricted pathology. Pooling the available studies allows investigation of covariate effects. Methods: Data from four studies investigating dexmedetomidine pharmacokinetics after i.v. administration (n = 95) were combined to undertake a population pharmacokinetic analysis of dexmedetomidine time–concentration profiles (730 observations) using nonlinear mixed effects modeling (NONMEM). Estimates were standardized to a 70‐kg adult using allometric size models. Results: Children had a mean age of 3.8 (median 3 years, range 1 week–14 years) and weight of 16.0 kg (median 13.3 kg, range 3.1–58.9 kg). Population parameter estimates (between subject variability) for a two‐compartment model were clearance (CL) 42.1 (CV 30.9%) l·h^?1·70 kg^?1, central volume of distribution (V1) 56.3 (61.3%) l·70 kg^?1, inter‐compartment clearance (Q) 78.3 (37.0%) l·h^?1·70 kg^?1 and peripheral volume of distribution (V2) 69.0 (47.0%) l·70 kg^?1. Clearance maturation with age was described using the Hill equation. Clearance increases from 18.2 l·h^?1·70 kg^?1 at birth in a term neonate to reach 84.5% of the mature value by 1 year of age. Children given infusion after cardiac surgery had 27% reduced clearance compared to a population given bolus dose. Simulation of published infusion rates that provide adequate sedation for intensive care patients found a target therapeutic concentration of between 0.4 and 0.8 μg·l^?1. Conclusions: The sedation target concentration is similar to that described for adults. Immature clearance in the first year of life and a higher clearance (when expressed as l·h^?1·kg^?1) in small children dictate infusion rates that change with age. Extrapolation of dose from children given infusion in intensive care after cardiac surgery may not be applicable to those sedated for noninvasive procedures out of intensive care.     

Postoperative morphine concentration in infants with or without biliary atresia and its association with hepatic blood flow

We measured pre‐operative hepatic blood flow and postoperative morphine concentration in infants with or without biliary atresia. Thirty‐four infants (0–3 months) with biliary atresia undergoing portoenterostomy (Kasai operation) were included and hepatic blood flow was assessed by magnetic resonance imaging before surgery in 12 of them. Sixteen subjects (0–3 months) without liver disease undergoing abdominal or pelvic surgery acted as controls and six of them had hepatic blood flow assessed. Intravenous morphine (8 μg.kg^?1.h^?1) was administered to all patients postoperatively. The median (IQR [range]) relative hepatic blood flow was 3.51 (2.72–3.88 [1.68–4.43]) with and 3.15 (2.66–4.42 [2.30–5.01]) without biliary atresia (p = 0.851). The median (IQR [range]) morphine concentration after 24 h infusion was 5.9 (4.5–16.4 [2.9–42.2]) ng.ml^?1 and 6.4 (3.2–12.0 [1.9–48.6]) ng.ml^?1, respectively (p = 0.460). An inverse regression relation was found between the morphine concentration and the hepatic perfusion index (R² = 0.519, p = 0.001). Compensatory increases in hepatic arterial blood flow maintain the total hepatic blood flow in infants with biliary atresia.     

Comparison of alemtuzumab vs. antithymocyte globulin induction therapy in primary non‐sensitized renal transplant patients treated with rapid steroid withdrawal

Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction therapy in renal transplantation. This retrospective, single‐center, cohort study evaluated cumulative incidence of one‐yr biopsy‐proven acute rejection (BPAR) among 200 consecutive primary non‐sensitized kidney transplant recipients who received either alemtuzumab (n = 100) or rATG (n = 100) induction followed by rapid steroid taper, tacrolimus, and mycophenolate mofetil. Protocol biopsies, plasma and urine BK virus PCR, serum creatinine and iothalamate glomerular filtration rate (iGFR), were obtained at 1, 4, and 12 months from transplantation. The one‐yr BPAR rates were similar between the alemtuzumab and rATG groups; however, rejection Banff IA and higher was more common in the alemtuzumab arm (18% vs. 5%, p = 0.047). After adjusting for confounding variables, alemtuzumab was still associated with Banff IA and higher rejection (adjusted OR: 3.7, CI: 1.2–10.5, p = 0.02). Despite similar rates of BK viremia, more patients in the alemtuzumab arm developed BK nephropathy (16% vs. 3%, p = 0.046). One‐year iGFR (53.4 ± 20.2 vs. 71.9 ± 27.2 mL/min/1.73 m², p = 0.002) and three‐yr graft survival (89.5% vs. 95%, p = 0.05) were lower in the alemtuzumab group. In low immunological risk kidney transplant recipients on steroid‐free immunosuppression, alemtuzumab was associated with more severe rejection and BK nephropathy compared to rATG.