Serum bupivacaine concentrations during continuous extrapleural infusion

Dauphin, A.; Gupta, Ram N.; Young, Jack; Morton, William D.

doi:10.1007/bf03014455

Cited by 29 publications

(11 citation statements)

References 16 publications

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“…Our data indicate that damage to the barrier function of the oral mucosa resulting from oral mucositis increases the systemic uptake of bupivacaine when administered locally in the oral cavity. However, the risk of systemic adverse reactions is minimal because the bupivacaine plasma levels in the patients with HNC were well below the toxic threshold, bearing in mind that we have measured the total plasma concentration of bupivacaine and not the free fraction of bupivacaine, which exerts pharmacological and toxicological effects . Patients with HNC often experience a reduced volume of saliva, leading to less saliva washout .…”

Section: Discussionmentioning

confidence: 99%

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis

Mogensen

Sverrisdóttir

Sveinsdóttir

et al. 2016

Basic Clin Pharma Tox

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Abstract:The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed-effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times higher in HNC patients with oral mucositis grade 3-4 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25-mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit.

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Section: Discussionmentioning

confidence: 99%

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis

Mogensen

Sverrisdóttir

Sveinsdóttir

et al. 2016

Basic Clin Pharma Tox

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“…2,8 Although the total bupivacaine plasma level steadily increased in surgical patients receiving postoperative infusion, the free bupivacaine level remained unchanged. 20 A postoperative rise in ␣ 1 -acid glycoprotein, which binds to the bupivacaine, appears to offer protection against toxicity. 20 The same may be true in patients with MFR due to trauma.…”

Section: Discussionmentioning

confidence: 99%

Continuous Thoracic Paravertebral Infusion of Bupivacaine for Pain Management in Patients With Multiple Fractured Ribs*

Karmakar

Critchley

et al. 2003

Chest

121

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“…The volumes of ropivacaine given were calculated so as to affect at least six dermatomes [18]. We did not infuse ropivacaine during surgery in order to avoid accumulation [19, 20]. The concentration of ropivacaine and its rate of administration after surgery were based on our previous experience with epidural analgesia following cardiac surgery [17].…”

Section: Discussionmentioning

confidence: 99%

Bilateral paravertebral blockade for conventional cardiac surgery

et al. 2003

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SummaryWe conducted a postal survey of cardiac anaesthetists in the UK, to determine the extent of magnesium sulphate (MgSO 4 ) use and the main indications for its administration. Questionnaires were sent to anaesthetists at 35 UK hospitals undertaking adult cardiac surgery. Responses were received from 24 hospitals (69%) totalling 124 individual responses. Twenty-five (20%) of the anaesthetists responding to the questionnaire routinely gave magnesium other than in cardioplegia. The most common indications for administration were arrhythmia prophylaxis and treatment, myocardial protection and the treatment of hypomagnesaemia.Keywords Anaesthesia; cardiovascular. Heart; arrhythmia, prevention. Ions; magnesium. Magnesium deficiency is common in hospitalised patients [1]. It may be related to diuretic and beta-blocker therapy, and is more common in the cardiac surgical population [2, 3]. Hypomagnesaemia is common following cardiopulmonary bypass (CPB), and persists into the postoperative period [4]. It is associated with a higher incidence of arrhythmias and a low cardiac index [2]. However, the routine administration of magnesium sulphate during cardiac surgery remains controversial. Several studies support its routine administration for arrhythmia prophylaxis [5][6][7][8], whereas others oppose this view [9, 10] and even suggest a detrimental effect from magnesium administration [11]. This survey was conducted to investigate the attitudes and current practice of cardiac anaesthetists in the UK to the routine administration of magnesium sulphate. MethodsFollowing approval from the Association of Cardiothoracic Anaesthetists (ACTA), postal questionnaires (Appendix) were sent to the ACTA contact in 35 adult cardiac surgery centres for distribution to consultant anaesthetists. The questionnaire was designed to examine the incidence of routine magnesium sulphate use, the dose and timing of its administration, the indications for its use, the frequency of serum magnesium measurements and the reasons for avoiding its routine use. ResultsReplies were received from 24 (69%) hospitals. A total of 124 individual questionnaires were completed. Of these, 25 (20%) of anaesthetists routinely administered magnesium sulphate.Of those who gave magnesium routinely, 76% administered it during CPB. The most common dose used was a 2-4 g (8-16 mmol) bolus. The main indications were arrhythmia prophylaxis, myocardial protection and suspected hypomagnesaemia associated with hypokalaemia and diuretic therapy. Several respondents commented on its usefulness in patients with poor left ventricular function and a reduction in inotropic support requirements post CPB.Thirty-six per cent of anaesthetists administer magnesium post CPB (24% during and post CPB), mainly as a bolus of 2-4 g. Indications given are arrhythmia prophylaxis and treatment, and measured hypomagnesaemia.Thirty-two per cent of anaesthetists administer it pre-CPB. A larger bolus dose of 5 g is most frequently given. The numerous indications stated include arrhythmia Anaesth...

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Serum bupivacaine concentrations during continuous extrapleural infusion

Cited by 29 publications

References 16 publications

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis

Continuous Thoracic Paravertebral Infusion of Bupivacaine for Pain Management in Patients With Multiple Fractured Ribs*

Bilateral paravertebral blockade for conventional cardiac surgery

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