Per-Arne Lönnqvist

Bilateral thoracic paravertebral block: potential and practice

Paravertebral nerve blocks (PVBs) can provide excellent intraoperative anaesthetic and postoperative analgesic conditions with less adverse effects and fewer contraindications than central neural blocks. Most published data are related to unilateral PVB, but its potential as a bilateral technique has been demonstrated. Bilateral PVB has been used successfully in the thoracic, abdominal, and pelvic regions, sometimes obviating the need for general anaesthesia. We have reviewed the use of bilateral PVB in association with surgery and chronic pain therapy. This covers 12 published studies with a total of 538 patients, and with varied methods and outcome measures. Despite the need for relatively large doses of local anaesthetics, there are no reports of systemic toxicity. The incidence of complications such as pneumothorax and hypotension is low. More studies on the use of bilateral PVB are required.

Positive end-expiratory pressure ventilation elicits increases in endogenously formed nitric oxide as detected in air exhaled by rabbits

Background Nitric oxide (NO) formed from L-arginine is exhaled by mammals and regulates pulmonary vascular tone. Little is known about how its formation is stimulated. Methods The concentration of NO in exhaled air was monitored by chemiluminescence in pentobarbital-anesthetized rabbits receiving mechanical ventilation by tracheostomy with graded positive end-expiratory pressure (PEEP). Results Introduction of PEEP (2.5-15 cmH2 O) elicited dose-dependent and reproducible increments in exhaled NO and in arterial oxygen tension (PaO2). The increase in exhaled NO exhibited a biphasic pattern, with an initial peak followed by a partial reversal during the 4-min period at each level of PEEP. Thus, at a PEEP of 10 cmH sub 2 O, exhaled NO initially increased from 19 plus/minus 4 to 30 plus/minus 5 parts per billion (ppb) (P < 0.001, n = 9) and then decreased to 27 plus/minus 5 ppb (P < 0.005) at the end of the 4-min observation period. Simultaneously, PaO2 increased from 75 plus/minus 12 mmHg in the control situation to 105 plus/minus 11 mmHg (P < 0.05) at a PEEP of 10 cmH2 O. After bilateral vagotomy, including bilateral transection of the depressor nerves, the increase in exhaled NO in response to PEEP was significantly reduced (P < 0.01). Thus, after vagotomy, a PEEP of 10 cmH2 O elicited an increase in the concentration of exhaled NO from 13 plus/minus 3 to 17 plus/minus 3 ppb (n = 7). Vagotomy did not affect the baseline concentration of NO in exhaled air. The PEEP-induced increments in PaO2 were not affected by the NO synthase inhibitor L-Nomega-arginine-methylester (30 mg *symbol* kg sup -1 intravenously). In open-chest experiments, PEEP (10 cmH2 O) induced a reduction in cardiac output from 317 plus/minus 36 to 235 plus/minus 30 ml *symbol* min sup -1 and an increase in exhaled NO from 23 plus/minus 6 to 30 plus/minus 7 ppb (P < 0.05, n = 5). Reduction in cardiac output from 300 plus/minus 67 to 223 plus/minus 52 ml *symbol* min sup -1 by partial obstruction of the pulmonary artery did not significantly increase exhaled NO (from 23 plus/minus 7 to 25 plus/minus 6, difference not significant; n = 3). Conclusions PEEP elicited increments in exhaled NO, perhaps by a stretch-dependent effect on the respiratory system. This finding may be attributed in part to a vagally influenced mechanism.

Inhaled nitric oxide therapy in neonates and children: reaching a European consensus

Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has subsequently been used extensively in the management of neonates and children with cardiorespiratory failure. This paper assesses evidence for the use of iNO in this population as presented to a consensus meeting jointly organised by the European Society of Paediatric and Neonatal Intensive Care, the European Society of Paediatric Research and the European Society of Neonatology. Consensus Guidelines on the Use of iNO in Neonates and Children were produced following discussion of the evidence at the consensus meeting.

Plasma Concentrations of Bupivacaine in Neonates After Continuous Epidural Infusion

This study reports plasma bupivacaine concentrations in 13 neonates who received lumbar epidural anesthesia during major abdominal surgery.A bolus of 1.8 mg/kg of bupivacaine (2.5 mg/mL) was administered after induction of anesthesia, followed by a continuous infusion of 0.2 mg [centered dot] kg-1 [centered dot] h-1 (1.25 mg/mL). Plasma concentrations of total and free bupivacaine and alpha 1-acid-glycoprotein (AAG) were determined. Results are presented as mean (+/- SEM). At 48 h, five of nine patients still had increasing total plasma concentrations, and the total bupivacaine concentrations ranged between 0.7 and 3.1 micro g/mL. The plasma levels of AAG increased significantly between 1 and 24 h (4.3 +/- 2.3 nM and 7.7 +/- 2.3 nM, respectively) (P = 0.018). The free concentrations of bupivacaine were relatively unchanged at 1 and 24 h (84 +/- 20 ng/mL and 58 +/- 15 ng/mL, respectively). No adverse events occurred during the study period. In conclusion, the dose administered in this study appears to be safe. However, a substantial number of patients still had increasing concentrations of total plasma bupivacaine at 48 h. Furthermore, the interindividual variation was considerable. These observations cause concern about the safety of epidural infusions longer than 48 h in the age group studied. (Anesth Analg 1997;84:501-5)

The place of premedication in pediatric practice.

Behind the multiple arguments for and against the use of premedication, sedative drugs in children is a noble principle that of minimizing psychological trauma related to anesthesia and surgery. However, several confounding factors make it very difficult to reach didactic evidence‐based conclusions. One of the key confounding issues is that the nature of expectations and responses for both parent and child vary greatly in different environments around the world. Studies applicable to one culture and to one hospital system (albeit multicultural) may not apply elsewhere. Moreover, the study of hospital‐related distress begins at the start of the patient’s journey and ends long after hospital discharge; it cannot be focused completely on just the moment of anesthetic induction. Taking an example from actual practice experience, the trauma caused by the actual giving of a premedication to a child who absolutely does not want it and may struggle may not be recorded in a study but could form a significant component of overall effect and later psychological pathology. Clearly, attitudes by health professionals and parents to the practice of routine pediatric premedication, vary considerably, often provoking strong opinions. In this pro–con article we highlight two very different approaches to premedication. It is hoped that this helps the reader to critically re‐evaluate a practice, which was universal historically and now in many centers is more selective.

Themed issue ‘Pediatric Regional Anesthesia’– starting 2012 with a bang!

Every busy clinician and academic is overloaded with dull and uninteresting tasks at times, but every so often you get the chance to do something really important. To have been appointed editor of this themed issue on Pediatric Regional Anesthesia (PRA) is truly fantastic, and I hope that it will be as well appreciated by the readership as the hugely successful issue on the Pediatric Airway in 2009 (1). In this special issue, you may find some minor overlap and perhaps some slightly opposing views, but I sincerely hope that both the novice and the seasoned veteran of PRA will find inspiration, food for thought, new ideas, and enthusiasm for future studies. Often, pediatric practice lags behind adult medicine, and it may well be wise to first try out new treatments in adults and learn about potential dangers and side effects, before subjecting the vulnerable population of infants and children to new medical wonders. However, sometimes our discipline moves fast when it is obvious that new treatments or techniques will definitely benefit our small patients, reducing suffering and mortality. Thus, even some of the initial patients reported in the seminal publication on spinal anesthesia by August Bier in 1899, were children, and it is now just over 100 years since Gray published the first large-scale case series with regard to the successful use of spinal anesthesia in children undergoing various surgical interventions (1909) (2). Against this background, this themed issue starts with an outstanding review of the history of PRA, written by an equally outstanding second-wave pioneer and promoter of this particular facet of pediatric anesthesia, Professor Emeritus Kester Brown (3). When the second and definitive push for PRA was started in the 1980s, concerns were raised (mainly in the United States) and manifested in the slogan ‘double anaesthesia, double the risk!’ Despite being utterly wrong, this outburst of healthy scepticism forced the proponents of PRA to perform scientific studies and provide evidence and consensus that PRA in fact is of great benefit to children. Bösenberg and Wolf (4,5) nicely summarized the positive effects of PRA, in terms of excellent intraand postoperative analgesia, evidence for improved outcome and beneficial effects on the surgical stress response in infants and children. To provide balance in the risk-benefit analysis, Claude Ecoffey demonstrates that PRA is well within reasonable and acceptable safety limits (6). He has been instrumental in conducting two prospective, large-scale French studies focussed on the safety of PRA (7,8). It is certainly very reassuring that in more than 50 000 patients, PRA was associated with a complication rate of only 1 : 1000 and that the complications that occurred did not result in any long-term sequelae. We all know that it is not the needle that blocks the nerves; it is in fact the solution that is injected close and around the nerve structures that produces the desired local anesthetic effect. During the last twenty years, two new long-acting local anesthetics have been introduced and a large number of adjunct drugs have also been suggested to prolong the effect of the local anesthetics. Another French expert, JeanXavier Mazoit, provides a very nice effort to clarify the issue of local anesthetics and their adjuncts from a pediatric perspective (9). My own contribution (10) deals with the potentially lethal complications of inadvertent intravascular injection of local anesthetic and the fairly recent treatment for systemic toxicity of local anesthetic drugs with the infusion of lipid emulsions. This new treatment option has proven very effective in adults, and successful use has also been reported in children during recent years. However, recent animal studies from the Zurich group question whether lipid is more effective than adrenaline in infants and children. Once again, ‘children are not small adults!’ (11). The range of PRA techniques is next described, starting with central neuraxial blocks in children. In three separate reviews, Jöhr, Moriarty and Kokki provide the fundamentals and the cutting edge of caudal, epidural, and spinal blocks in children (12–14). A clear and current trend in the second French study, as well as some other recent publications, indicates a shift from central neuraxial blocks to peripheral nerve blocks, especially in children <3 years of age (8). This fact most surely can be attributed to the recent revolution concerning ultrasound-guided regional anesthesia. Furthermore, peripheral nerve blocks have been shown to be associated with an even better safety profile than central blocks (8). Thus, the details of various peripheral nerve block techniques are presented by Flack, Anderson, Suresh, and the members of the Marhofer Vienna PRA group (15–18). Prolonging peripheral blocks by continuous peripheral catheter techniques have been helped by ultrasound guidance and equipment development. The Montpeillier group has been in the very forefront of

Paravertebral vs epidural block in children. Effects on postoperative morphine requirement after renal surgery.

Continuous thoracic paravertebral blockade (PVB) has only recently been reported in pediatric patients. The aim of the present study was to compare retrospectively the postoperative analgesic efficacy of PVB vs conventional lumbar epidural blockade (EDA) in children. Thirty–five consecutive pediatric patients undergoing renal surgery, receiving either PVB (n = 15) or EDA (n = 20), were reviewed. The need for supplemental morphine administration during the first 24 postoperative hours was used to assess the postoperative analgesic efficacy of the two different regional techniques. Both the total amount of supplemental morphine and the number of patients with no need for supplemental morphine administration, were compared between the two groups. The need for supplemental morphine administration was significantly lower (P = 0.046) and the number of patients with no need for supplemental morphine administration postoperatively was significantly higher (P = 0.019) in patients treated with PVB vs EDA. The present study indicates that PVB may possess a potential for postoperative analgesia equal to or maybe even superior to conventional lumbar EDA in pediatric patients undergoing renal surgery. Further prospective studies investigating the analgesic efficacy of this novel technique are warranted.

Midazolam as premedication: Is the emperor naked or just half‐dressed?

The question of whether premedication should be routinely used in pediatric patients has recently been the focus of debate among pediatric anesthetists. Although most of us have accepted to use a more individualized approach regarding premedication, many of us still continue to use it in a significant proportion of pediatric patients. However, one remaining question in this context is, which drug or what combination of drugs should be used in order to best achieve our goals and to minimize potential side effects. Looking back at the premedication routines, when the authors started their anesthesia careers, a large number of different drugs or drug combinations were used and each individual department, or even different sections within the department, had their own ‘home-made recipes’, none of which was evidence based. If there had been one favorable alternative that option would most probably have taken precedence as the standard treatment. In this situation a new ‘wonder drug’ was launched in the mid-1980s and was immediately promoted both by opinion leaders and the pharmaceutical company. This new drug was called midazolam and was claimed to possess a number of highly desirable effects in the setting of premedication. A clever sales strategy combined with a slightly uncritical willingness of clinicians to adopt this new drug for premedication purposes soon turned it into a ‘gold standard’ situation and midazolam was considered by many as the greatest advance. Unfortunately, the routine use of midazolam for pediatric premedication has never been critically evaluated and the aim of the present editorial is to put a number of the proposed benefits of this drug into a more balanced perspective.

Pharmacokinetics of Clonidine after Rectal Administration in Children

Backgroundα2 Agonists have been shown to produce desirable effects when used as premedication or as an adjunct to general anesthesia in adult patients. Several of these beneficial effects (e.g., reduced anesthetic requirements and analgesia without respiratory depression) would be of great benefit in pediatric anesthesia. Information regarding the use of α2 agonists in children is largely lacking. The aim of this study was to investigate the pharmacokinetics of clonidine after rectal administration in children. MethodsTen ASA physical status 1 pediatric patients (age 14–48 months, weight 10–20 kg) received 2.5 μg·kg-1 of clonidine by the rectal route. Blood samples were taken during a 24-h period after the administration. Plasma levels of clonidine were analyzed by radioimmunoassay and subjected to a computer-aided curve-fitting program (PC Nonlin). To estimate the bioavailability of clonidine the results from the current study were compared with data from a previous study in which the same dose of clonidine was given to a similar patient population by the Intravenous route. ResultsMaximum plasma concentration was 0.77 ng· ml-1(0.62–0.88), time to maximum plasma concentration 51 min (29–70), terminal half-life 12.5 h (8.7–19.5), and bioavailability 95% (73–119) (medians [95% confidence interval]). Plasma concentrations within the adult clinically effective range (0.2–2.0 ng·ml-1) were obtained within 10 min of administration. ConclusionsRectal administration of 2.5 μg· kg-1 of clonidine in children, approximately 20 min before induction of anesthesia, achieves plasma concentrations within the range known to be clinically effective in adults.

Clonidine disposition in children; a population analysis.

Background:  There are few data describing clonidine population pharmacokinetics in children (0–15 years) despite common use. Current pediatric data, described in terms of elimination half‐life or Cmax and Tmax, poorly explain variability in drug responses among individuals representative of those in whom the drug will be used clinically.