Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children.

Abstract:

BACKGROUND:Descriptions of the pharmacokinetics and metabolism of morphine and its metabolites in young children are scant. Previous studies have not differentiated the effects of size from those related to age during infancy. METHODS:Postoperative children 0-3 yr old were given an intravenous loading dose of morphine hydrochloride (100 micro g kg(-1) in 2 min) followed by either an intravenous morphine infusion of 10 micro g h(-1) kg(-1) (n=92) or 3-hourly intravenous morphine boluses of 30 micro g kg(-1) (n=92). Additional morphine (5 micro g kg(-1)) every 10 min was given if the visual analogue (VAS, 0-10) pain score was >/=4. Arterial blood (1.4 ml) was sampled within 5 min of the loading dose and at 6, 12 and 24 h for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). The disposition of morphine and formation clearances of morphine base to its glucuronide metabolites and their elimination clearances were estimated using non-linear mixed effects models. RESULTS:The analysis used 1856 concentration observations from 184 subjects. Population parameter estimates and their variability (%) for a one-compartment, first-order elimination model were as follows: volume of distribution 136 (59.3) litres, formation clearance to M3G 64.3 (58.8) litres h(-1), formation clearance to M6G 3.63 (82.2) litres h(-1), morphine clearance by other routes 3.12 litres h(-1) per 70 kg, elimination clearance of M3G 17.4 (43.0) litres h(-1), elimination clearance of M6G 5.8 (73.8) litres h(-1). All parameters are standardized to a 70 kg person using allometric 3/4 power models and reflect fully mature adult values. The volume of distribution increased exponentially with a maturation half-life of 26 days from 83 litres per 70 kg at birth; formation clearance to M3G and M6G increased with a maturation half-life of 88.3 days from 10.8 and 0.61 litres h(-1) per 70 kg respectively at birth. Metabolite formation decreased with increased serum bilirubin concentration. Metabolite clearance increased with age (maturation half-life 129 days), and appeared to be similar to that described for glomerular filtration rate maturation in infants. CONCLUSION:M3G is the predominant metabolite of morphine in young children and total body morphine clearance is 80% that of adult values by 6 months. A mean steady-state serum concentration of 10 ng ml(-1) can be achieved in children after non-cardiac surgery in an intensive care unit with a morphine hydrochloride infusion of 5 micro g h(-1) kg(-1) at birth (term neonates), 8.5 micro g h(-1) kg(-1) at 1 month, 13.5 micro g h(-1) kg(-1) at 3 months and 18 micro g h(-1) kg(-1) at 1 year and 16 micro g h(-1) kg(-1) for 1- to 3-yr-old children.

journal_name

Br J Anaesth

authors

Bouwmeester NJ,Anderson BJ,Tibboel D,Holford NH

doi

10.1093/bja/aeh042

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

208-17

issue

2

eissn

0007-0912

issn

1471-6771

pii

S0007-0912(17)36189-5

journal_volume

92

pub_type

临床试验,杂志文章,随机对照试验
  • Impact of balanced tetrastarch raw material on perioperative blood loss: a randomized double blind controlled trial.

    abstract:BACKGROUND:As 6% hydroxyethyl starch (HES) 130/0.40 or 130/0.42 can originate from different vegetable sources, they might have different clinical effects. The purpose of this prospective, randomized, double-blind controlled trial was to compare two balanced tetrastarch solutions, one maize-derived and one potato-deriv...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/bja/aew249

    authors: Joosten A,Tircoveanu R,Arend S,Wauthy P,Gottignies P,Van der Linden P

    更新日期:2016-10-01 00:00:00

  • Double burst stimulation (DBS): a new pattern of nerve stimulation to identify residual neuromuscular block.

    abstract::We present a new pattern of nerve stimulation--double burst stimulation (DBS)--to detect residual neuromuscular block manually. The DBS consists of two short lasting, 50-Hz tetanic stimuli or bursts separated by a 750-ms interval. The response to this pattern of stimulation is two single separated muscle contractions ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/62.3.274

    authors: Engbaek J,Ostergaard D,Viby-Mogensen J

    更新日期:1989-03-01 00:00:00

  • Evaluation of three preparations of etomidate.

    abstract::Three formulations of etomidate were evaluated in unpremedicated patients undergoing minor gynaecological procedures. There was a high frequency of pain on injection (up to 50%) and excitatory phenomena (up to 95%) with all formulations. The frequency of excitatory phenomena was significantly greater than that after m...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章

    doi:10.1093/bja/50.9.925

    authors: Zacharias M,Clarke RS,Dundee JW,Johnston SB

    更新日期:1978-09-01 00:00:00

  • Nerve injury by needle nerve perforation in regional anaesthesia: does size matter?

    abstract:BACKGROUND:In regional anaesthesia, there is a risk of direct nerve injury. The purpose of this study was to determine whether the diameter of the applied needle is associated with the magnitude of nerve injury after needle nerve perforation. METHODS:In five anaesthetized pigs, the brachial plexus were exposed bilater...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aep366

    authors: Steinfeldt T,Nimphius W,Werner T,Vassiliou T,Kill C,Karakas E,Wulf H,Graf J

    更新日期:2010-02-01 00:00:00

  • Determination of residual antiplatelet activity of clopidogrel before neuraxial injections.

    abstract:BACKGROUND:Guidelines recommend discontinuation of clopidogrel for 7 days before a neuraxial injection, while other directives suggest that 5 days might be adequate. We examined the time course of antiplatelet activity after clopidogrel discontinuation in patients undergoing epidural injections. METHODS:Thirteen patie...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aer298

    authors: Benzon HT,McCarthy RJ,Benzon HA,Kendall MC,Robak S,Lindholm PF,Kallas PG,Katz JA

    更新日期:2011-12-01 00:00:00

  • Fatal cardiac tamponade as a result of a peripherally inserted central venous catheter: a case report and review of the literature.

    abstract::We present a case of fatal cardiac tamponade that occurred in association with a peripherally inserted central catheter (PICC) inserted from the right antecubital fossa. Migration of the catheter from the right atrium within 24 h of insertion lead to the administration of a potassium-enriched sodium chloride solution ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aem181

    authors: Orme RM,McSwiney MM,Chamberlain-Webber RF

    更新日期:2007-09-01 00:00:00

  • Feedback system to estimate the quality of outpatient preoperative evaluation records: an analysis of end-user satisfaction.

    abstract:BACKGROUND:During preanaesthesia evaluation at an outpatient clinic, information is summarized and structured. We aimed to estimate the effectiveness of this process by determining the proportion of patients presenting for surgery who had valid preoperative anaesthesia assessment records, and also the proportion of pat...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aeq200

    authors: van Klei WA,Peelen LM,Kruijswijk JE,van Wolfswinkel L

    更新日期:2010-11-01 00:00:00

  • Cerebrovascular effects of isoflurane in man. Intracranial pressure and middle cerebral artery flow velocity.

    abstract::Twelve hydrocephalic patients undergoing hydrodynamic studies and shunt procedures during general anaesthesia were subjected to short term observations of the cerebrovascular effects of isoflurane. Intraventricular pressure (IVP), arterial pressure (AP); cerebral perfusion pressure (CPP = AP-IVP), end-tidal PCO2, Cere...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/59.10.1208

    authors: Lundar T,Lindegaard KF,Refsum L,Rian R,Nornes H

    更新日期:1987-10-01 00:00:00

  • Comparison between pressures measured from the proximal external jugular vein and a central vein.

    abstract::Mean venous pressures were measured in 20 patients in whom a catheter, inserted via the external jugular vein, failed to pass centrally. The catheter used had a rounded end and two side holes. Pressures were measured with the patient's head in three different positions. The pressures were compared with the central ven...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/58.12.1384

    authors: Shah MV,Swai EA,Latto IP

    更新日期:1986-12-01 00:00:00

  • Comparison of S(-)-bupivacaine with racemic (RS)-bupivacaine in supraclavicular brachial plexus block.

    abstract::Bupivacaine is used widely as a local anaesthetic but has potential for severe cardiovascular and central nervous system (CNS) toxicity. It has an asymmetric carbon atom giving it a chiral centre, and the commercial preparation is a racemic mixture of its two enantiomers: dextro or R(+)-bupivacaine and levo or S(-)-bu...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/80.5.594

    authors: Cox CR,Checketts MR,Mackenzie N,Scott NB,Bannister J

    更新日期:1998-05-01 00:00:00

  • Randomized trial of red cell washing for the prevention of transfusion-associated organ injury in cardiac surgery.

    abstract:Background:Experimental studies suggest that mechanical cell washing to remove pro-inflammatory components that accumulate in the supernatant of stored donor red blood cells (RBCs) might reduce inflammation and organ injury in transfused patients. Methods:Cardiac surgery patients at increased risk of large-volume RBC ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1093/bja/aex083

    authors: Wozniak MJ,Sullo N,Qureshi S,Dott W,Cardigan R,Wiltshire M,Morris T,Nath M,Bittar N,Bhudia SK,Kumar T,Goodall AH,Murphy GJ

    更新日期:2017-05-01 00:00:00

  • Pharmacokinetics of glycopyrronium in uraemic patients.

    abstract::We studied the pharmacokinetics of glycopyrronium in 11 uraemic patients undergoing cadaveric renal transplantation and in seven ASA I control patients undergoing general surgery. Glycopyrronium 4 micrograms kg-1 was given i.v. before induction of anaesthesia. Blood and urine samples were collected for up to 24 h for ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/71.3.437

    authors: Kirvelä M,Ali-Melkkilä T,Kaila T,Iisalo E,Lindgren L

    更新日期:1993-09-01 00:00:00

  • Pharmacokinetics of intravenous emulsified isoflurane in beagle dogs.

    abstract:BACKGROUND:We previously demonstrated that i.v. emulsified isoflurane induces general anaesthesia in animals. In this study, we compared the pharmacokinetics of emulsified isoflurane given as i.v. bolus and as infusion in beagle dogs. METHODS:Sixteen beagle dogs were assigned randomly to a bolus group comprising three...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aes311

    authors: Yang XL,Zhang WS,Liu J,Yang ZB,Jiang XH

    更新日期:2013-01-01 00:00:00

  • Tetanic stimulus of ulnar nerve as a predictor of heart rate response to skin incision in propofol remifentanil anaesthesia.

    abstract:BACKGROUND:To study adequate antinociception during general anaesthesia, tetanic stimulus of 5-10 s duration has been used previously as a standardized nociceptive stimulus. However, such stimuli have been found to correlate poorly with intraoperative nociception. We hypothesized that an electrical tetanic stimulus of ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/bja/aem200

    authors: Rantanen M,Yppärilä-Wolters H,van Gils M,Yli-Hankala A,Huiku M,Kymäläinen M,Korhonen I

    更新日期:2007-10-01 00:00:00

  • Comparison of intubating laryngeal mask airway and Bullard laryngoscope for oro-tracheal intubation in adult patients with simulated limitation of cervical movements.

    abstract:BACKGROUND:Intubation of a patient with limited cervical spine movement or in whom movement of the cervical spine is not desirable is always a challenge even to the most experienced anaesthesiologist. The intubating laryngeal mask airway (ILMA) and the Bullard laryngoscope (BL) are two instruments recommended for endot...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/bja/aem127

    authors: Nileshwar A,Thudamaladinne A

    更新日期:2007-08-01 00:00:00

  • Effect of halothane, isoflurane and fentanyl on spectral components of heart rate variability.

    abstract::We have examined the effect of isoflurane, halothane and fentanyl on heart rate variability (HRV) using power spectral analysis (PSA). Forty patients were allocated randomly to receive one of four anaesthetic techniques. Anaesthesia was induced with propofol 2 mg kg-1 and all patients breathed a mixture of 66% nitrous...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/72.2.177

    authors: Galletly DC,Westenberg AM,Robinson BJ,Corfiatis T

    更新日期:1994-02-01 00:00:00

  • A comparison of dexmedetomidine, and alpha 2-adrenoceptor agonist, and midazolam as i.m. premedication for minor gynaecological surgery.

    abstract::The effects of i.m. dexmedetomidine 1.0 micrograms kg-1, a new alpha 2-adrenoceptor agonist, were compared with those of i.m. midazolam 0.08 mg kg-1 and placebo on vigilance, anaesthetic requirements, haemodynamic state and plasma catecholamine concentrations in a double-blind placebo-controlled study in 107 healthy (...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/67.4.402

    authors: Aantaa R,Jaakola ML,Kallio A,Kanto J,Scheinin M,Vuorinen J

    更新日期:1991-10-01 00:00:00

  • Development of a Core Outcome Set for studies evaluating the effects of anaesthesia on perioperative morbidity and mortality following hip fracture surgery.

    abstract:BACKGROUND:Perioperative studies of patients following hip fracture have large heterogeneity within their reported outcomes. This study aimed to develop a core outcome set for use in perioperative studies comparing the types of anaesthesia for hip fracture surgery. METHODS:The consensus process consisted of a systemat...

    journal_title:British journal of anaesthesia

    pub_type: 共识发展会议,杂志文章

    doi:10.1016/j.bja.2018.08.017

    authors: O'Donnell CM,Black N,McCourt KC,McBrien ME,Clarke M,Patterson CC,Blackwood B,McAuley DF,Shields MO

    更新日期:2019-01-01 00:00:00

  • Analysis of individual patient data from clinical trials: epidural morphine for postoperative pain.

    abstract:BACKGROUND:Individual patient information from clinical trials is infrequently available, but can provide insights for clinical trials and practice. METHODS:We analysed individual patient information from five randomized trials (913 patients) of i.v. patient-controlled analgesia (IVPCA) plus epidural placebo, morphine...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,meta分析

    doi:10.1093/bja/aep300

    authors: Mhuircheartaigh RJ,Moore RA,McQuay HJ

    更新日期:2009-12-01 00:00:00

  • Doing a good job and getting something good out of it: on stress and well-being in anaesthesia.

    abstract::The anaesthetist's work, aimed at giving safe anaesthesia to patients, can do both harm and good to the anaesthetist. Research on stress in anaesthesia has traditionally focused on how the negative effects of stress can be avoided and much effort has been put into improving anaesthetists' work environment to reduce th...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,评审

    doi:10.1093/bja/aeq125

    authors: Larsson J,Sanner M

    更新日期:2010-07-01 00:00:00

  • Effect of adrenaline on venous plasma concentrations of bupivacaine after interpleural administration.

    abstract::Bupivacaine 2.5 mg kg-1 (0.5 ml kg-1 of 0.5% solution), with or without adrenaline 5 micrograms ml-1, was administered by interpleural injection to 12 patients after elective cholecystectomy. Noncompartmental analysis indicated that the addition of adrenaline had no effect on total body clearance, apparent volume of d...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/64.6.662

    authors: Gin T,Chan K,Kan AF,Gregory MA,Wong YC,Oh TE

    更新日期:1990-06-01 00:00:00

  • Fentanyl and midazolam anaesthesia for coronary bypass surgery: a clinical study of bispectral electroencephalogram analysis, drug concentrations and recall.

    abstract::Bispectral index (BIS) was assessed as a monitor of depth of anaesthesia during fentanyl and midazolam anaesthesia for coronary bypass surgery. In 10 patients given morphine premedication, anaesthesia was induced with a combination of midazolam and fentanyl and thereafter maintained with a continuous infusion of a mix...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章

    doi:10.1093/oxfordjournals.bja.a013587

    authors: Barr G,Anderson RE,Samuelsson S,Owall A,Jakobsson JG

    更新日期:2000-06-01 00:00:00

  • Effect of riluzole on acute pain and hyperalgesia in humans.

    abstract::Riluzole modulates several transmitter systems which may be involved in nociception. Antinociceptive effects have been shown in animal studies, but there are no human data. Therefore, we have examined the acute analgesic effect of riluzole in a human model of inflammatory pain induced by a thermal injury on the distal...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/82.5.718

    authors: Hammer NA,Lillesø J,Pedersen JL,Kehlet H

    更新日期:1999-05-01 00:00:00

  • Frailty assessment: from clinical to radiological tools.

    abstract::Frailty is a syndrome of cumulative decline across multiple physiological systems, which predisposes vulnerable adults to adverse events. Assessing vulnerable patients can potentially lead to interventions that improve surgical outcomes. Anaesthesiologists who care for older patients can identify frailty to improve pr...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,评审

    doi:10.1016/j.bja.2019.03.034

    authors: Bentov I,Kaplan SJ,Pham TN,Reed MJ

    更新日期:2019-07-01 00:00:00

  • Descending aortic blood flow during aortic cross-clamp indicates postoperative splanchnic perfusion and gastrointestinal function in patients undergoing aortic reconstruction.

    abstract:BACKGROUND:The purpose of this observational study was to investigate the relationship between splanchnic and renal blood flow during infrarenal aortic cross-clamp (XC) and postoperative gastrointestinal perfusion and function. METHODS:Descending aortic blood flow (DABF) was continuously monitored with an oesophageal ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aes095

    authors: Kotake Y,Yamada T,Nagata H,Takeda J,Shimizu H

    更新日期:2012-06-01 00:00:00

  • Effect of intravenous parecoxib on post-craniotomy pain.

    abstract:BACKGROUND:Pain management in craniotomy patients is challenging, with mild-to-moderate pain intensity, moderate-to-high risk of postoperative nausea and vomiting (PONV), and potentially catastrophic consequences of analgesic-related side-effects. The aim of this study was to determine whether i.v. parecoxib administer...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/aer223

    authors: Williams DL,Pemberton E,Leslie K

    更新日期:2011-09-01 00:00:00

  • Effects of minor surgery and endotracheal intubation on postoperative breathing patterns in patients anaesthetized with isoflurane or sevoflurane.

    abstract::We studied the effects of minor surgery and endotracheal intubation on postoperative breathing patterns. We measured breathing patterns and laryngeal resistance during the periods immediately before intubation (preoperative) and immediately after extubation following minor surgery (postoperative) in eight patients ana...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/bja/87.5.706

    authors: Tanaka A,Isono S,Sato J,Nishino T

    更新日期:2001-11-01 00:00:00

  • Comparison of esCCO and transthoracic echocardiography for non-invasive measurement of cardiac output intensive care.

    abstract:BACKGROUND:The esCCO monitor (ECG- estimated Continuous Cardiac Output, Nihon Kohden(®)) is a new non-invasive tool for estimating cardiac output (CO). It derives CO from the pulse wave transit time (PWTT) estimated by the ECG and the plethysmographic wave. An initial calibration is needed to refine the relation linkin...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aes298

    authors: Bataille B,Bertuit M,Mora M,Mazerolles M,Cocquet P,Masson B,Moussot PE,Ginot J,Silva S,Larché J

    更新日期:2012-12-01 00:00:00

  • Anaesthesia and sleep apnoea.

    abstract::Sleep disordered breathing is a common problem affecting all age groups, particularly in association with certain other medical conditions and syndromes. The pathological consequences of the disorder may be severe, with significant implications for the perioperative management of sufferers. Research into the effects o...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,评审

    doi:10.1093/bja/86.2.254

    authors: Loadsman JA,Hillman DR

    更新日期:2001-02-01 00:00:00

  • Enhanced antinociceptive efficacy of epidural compared with i.v. methadone in a rat model of thermal nociception.

    abstract:BACKGROUND:The properties of methadone suggest a potential advantage for epidural over i.v. administration for pain relief, but little supportive evidence exists. METHODS:To investigate the pharmacokinetic and the pharmacodynamic properties of epidural and i.v. methadone, four doses of methadone (0.1, 0.25, 0.5, and 0...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章

    doi:10.1093/bja/aet234

    authors: Haroutiunian S,Kagan L,Yifrach-Damari I,Davidson E,Ratz Y,Hoffman A

    更新日期:2014-01-01 00:00:00