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Literature Reviews


The Incidence of Emergence Agitation Associated with Desflurane Anesthesia in Children is Reduced by Fentanyl

Cohen I, Hannallah R, Hummer K. Anesthesia & Analgesia 2001; 93: 88-91.

Review: The goal of this study was to determine the mean effective dose of fentanyl necessary to reduce the incidence of emergence agitation while preserving rapid recovery from general anesthesia with desflurane. The study consisted of 32 children, aged 2 - 9 years, American Society of Anesthesiologists physical status I or II, undergoing adenoidectomy with or without bilateral myringotomy and insertion of tubes.

Premedication was not administered to the study group. An inhalation induction consisting of nitrous oxide and oxygen (70%:30%) and sevoflurane was the technique of choice. Following placement of an intravenous catheter, mivacurium was used to facilitate endotracheal intubation. Anesthesia maintenance consisted of desflurane 4% - 6%, nitrous oxide 2L/min and oxygen

1L/min. Patients were assigned to one of four groups. Each patient received one of four doses of fentanyl: 1.25, 1.87, 2.8, or 4.2mcg/kg. The dose was determined by the previous patient's dose and response. The first patient received the smallest dose, 1.25mcg/kg. The study incorporated the classic up-down method (i.e., if the previous patient's response was positive, then the next lower dose was given, and if the response was negative, then the next larger dose was administered) to determine the effective fentanyl dose.

There was no control group.

At the completion of surgery, desflurane and nitrous oxide were discontinued simultaneously. A blinded observer assessed several criteria: time to first cough, facial grimacing and gagging, purposeful movement, eye opening, and extubation. In addition, discharge times from the PACU to the short-stay recovery unit (SSRU) and from the SSRU to home were recorded.

Following final analysis of the four doses of fentanyl; this study showed that a dose of 2.5mcg/kg of fentanyl, given after induction, successfully reduces the incidence of severe agitation associated with desflurane anesthesia in children without delaying emergence. An additional finding in this study, was the incidence of vomiting was found to be 75%.

Comments: This study is the first to look at the actual dose of fentanyl that will have an impact on decreasing the incidence of emergence agitation in children undergoing an adenoidectomy. It comes as no surprise that the use of supplemental fentanyl with desflurane would be effective in reducing agitation. Previous studies have examined the concurrent use of midazolam or propofol, but were found not to effectively reduce emergence agitation. The results of the study are worth consideration, and
can be incorporated in the busy operating room setting. However, one may also want to consider an antiemetic with this technique. Further studies still have to be done regarding the cause or causes of emergence agitation.

Reviewed by: Cheryl K. Gooden, MD, Mount Sinai Medical Center New York, NY


A Prospective Randomized Controlled Study of the Efficacy of Ketamine For Post Operative Pain Relief In Children After Adenotonsillectomy.

R L Aspinall and A Mayor. Paediatric Anaesthesia 2001;11: 333-336

The aim of this study was to determine if ketamine following adenotonsillectomy in children provided as safe and effective analgesia as morphine. The study group was comprised of 50 children, ages 1 to 16 years, admitted for routine adenotonsillectomy. All patients were anesthetized using a sleep dose of propofol and mivacurium, 0.2 mg/kg to facilitate intubation. All received 1 mg/kg of diclofenac per rectum after induction. None received any premedication or antiemetic. Anesthesia was maintained with oxygen, nitrous oxide, and isoflurane. Once the muscle relexant wore off, patients were allowed to breathe spontaneously. All patients were extubated while under deep anesthesia, and an oral airway was used as necessary. Patients were randomized to receive morphine, 0.1 mg/kg or ketamine, 0.5 mg/kg. Time to supplementary analgesia, defined as achieving a pain score of 4 or more, was used to compare the two groups. At pain scores of 4-6 patients received 20mg/kg of paracetamol, while score above 6 the patients received 0.1 mg/kg of morphine.

Comments: The treatment groups were well matched for age, weight, and duration of surgery. There were no differences between treatment groups for heart rate, respiration rate, blood pressure, or emergence phenomena. There was no statistical difference in time to supplementary analgesia between the two groups. The median time in the morphine group was 45 minutes, range 2-120, and in the ketamine group the median time was 100 minutes, range 8-120. When the data were analyzed as mean + standard error of the mean there was no difference in the time to supplementary analgesia. These findings suggest that ketamine and morphine in the doses administered provide similar postoperative analgesia. Nearly half of the patients in both groups had postoperative vomiting, but the authors have no comment on this finding even though the numbers are above average. The authors avoided the use of any antiemetic, fearing that it would mask postoperative bleeding from the tonsillar bed. Perhaps this fear is exaggerated. About 2% of children who present for adenotonsillectomy have obstructive apneic syndrome. Ketamine preserves upper airway tone and respiratory drive. Hence, in the subgroup of children with obstructive apneic syndrome, ketamine may prove a better analgesic then morphine, which may further depress the respiratory drive. This study did not consider patients with compromised respiration. Further studies are required to look at pediatric patients who suffer from sleep apnea and obstructive airway syndrome. A look at Ketamine to provide postoperative analgesia in general may also prove interesting.

Reviewed by: Hoshi J. Khambatta, MD, Babies & Children's Hospital, Columbia Presbyterian Medical Center, NY


Prediction of difficult airway in school-aged patients with microtia

Uezono S, Holtzman RS, Goto T, et al. Paediatric Anaesthesia 2001: 11:409-13.

Review: Because the mandible and external ear are derived from the 1st and 2nd branchial arch and cleft, respectively, the authors hypothesized that children with microtia would be more likely to be difficult to intubate when undergoing first stage cartilage reconstruction of the auricle. Ninety-three school aged children (mean age 10.5 years) with uni- or bilateral microtia were compared with 93 normal age-matched controls for :

a. frequency of difficult intubation (1=all of glottis visualized, 2=posterior commissure only, 3= epiglottis only, 4= neither glottis or epiglottis visualized)
b. number of conventional attempts at intubation and ultimate technique used
c. the relationship between degree of difficulty intubating and the number of other "OMENS" facial manifestations present of the hemifacial microsomy syndrome (HFM or Goldenhar syndrome)

Eighty-one patients (87%) had unilateral and twelve (13%) had bilateral microtia. The incidence of difficult intubation (class 3 or 4) was 2% and 42% for unilateral and bilateral microtia, respectively (p=0.0003; NS between unilateral vs controls). Of the 5 patients with bilateral microtia who were difficult to intubate, 1 was intubated blindly, 2 by lightwand, and 2 fiberoptically. All patients with difficult laryngoscopy had an abnormal mandible. Additional facial abnormalities were more often seen in patients with bilateral rather than unilateral microtia, and as the number of anomalies present in a given patient increased, the likelihood of difficult intubation also increased.

Discussion: The authors attribute difficult intubation associated with bilateral microtia to a deficiency of the submandibular space volume, with resultant decreased ability to displace the tongue and anterior pharyngeal tissues during laryngoscopy. The presence of mandibular abnormalities had a 100% sensitivity and 96% specificity for predicting difficult laryngoscopy. Microtia, was sensitive but not specific. The associated anomalies that compose the OMENS syndrome are: abnormal size/position of the orbit, mandibular abnormalities, microtia, facial nerve weakness or soft tissue deficiency. In the study, an abnormal mandible was defined as being small by gross exam, or having a radiographically abnormal ramus or condyle. Clinicians should be aware that nearly half of children with bilateral microtia are difficult to intubate, and as the number of associated anomalies of hemifacial microsomia syndrome increase, so does the likelihood of difficult intubation.

Reviewed by: Samuel E. Golden, MD, FAAP, Loyola University, Chicago, IL


Unlicensed and off label analgesic use in paediatric pain management

Conroy S and Peden V., Paediatric Anaesthesia 2001 11:431-436

The authors have undertaken a prospective four-week trial to examine the prescribing of analgesics in children. They have attempted to identify off label and unlicensed use of analgesics in children in their hospital. Of the 480 prescriptions for postoperative analgesics, 67% were used as indicated, and 33% were in an off label manner. The percentage of off label use reported is probably lower than current prescribing practices in the United States. Although the authors use different definitions for licensed or unlicensed use in the UK vs. the USA (e.g. morphine adult preparation), their definition does not alter the significance of their findings. More traditional agents such as acetaminophen (paracetamol), ibuprofen and codeine were much more frequently used as labeled (70-91%) compared to diclofenac, pethidine and morphine (2-21% on label use). Variability in preparation of agents and approved routes of administration were frequently the cited issues in off label use. This article did not address the increasingly frequent use of herbal or alternative medications in children which we have noted in the past decade.

On a daily basis, thousands of children are prescribed medications, which have been insufficiently examined in pediatric trials, and dosage recommendations are based on extrapolations from adult dosing patterns. This is in dire need of change. We have experienced the delay in the formulation of an oral midazolam suspension for years and relied on the intravenous preparation for our p.o. and p.r. administration. As individual physicians advocating for children, and as a Society, we must add our voices to the AAP and other organizations, which advocate for children and ensure further development of pharmaceutical trials desperately needed to improve pharmaceutical and technologic development availability for children.

Reviewed by: Joseph R. Tobin, MD, Wake Forest University School of Medicine, Durham, NC

Caudal bupivicaine-tramadol combination for postoperative analgesia in pediatric herniorrhaphy.

Senel AC, Akyol A, Dohman D, Solak M. ACTA Anaesthesiologica Scandinavica 2001; 45: 786-789.

Review: In this randomized single blinded prospective study, the authors examined the efficacy of caudally administered tramadol in reducing postoperative pain associated with inguinal surgery. Tramadol is a novel mu-1 opioid receptor agonist that is purported to lack the respiratory depressant effects of other less specific opioids. 60 boys age 12- 84 months undergoing unilateral hernia repair were randomized to one of three groups. All children received a standardized anesthetic regiment which included no premedication, mask general anesthesia, and administration of a caudal with study drug. The three study groups were based on the drug adminstered for caudal blockade, either bupivicaine 0.25% 1ml/kg (B), tramadol 1.5mg/kg in normal saline (T), or bupivicaine 0.25% 1 ml/kg mixed with tramadol 1.5mg/kg (B/T).

The results showed that patients who received B/T had a significantly longer time period to administration of first analgesic (13.5 ± 2.0h) than either the B group (9.8 ± 2.2h) or the T group (4.7 ± 1.4h). Also, patients who received T alone required more analgesics and had higher pain scores at 4 and 6h when compared to the other two groups. There was no difference in side effects between groups. The authors thus conclude that the addition of tramadol to bupivicaine for caudal blockade results in a longer period with out demand for additional analgesic compared with caudal bupivicaine alone with no increase in side effects.

Comments: Although tramadol is not yet (or just receiving approval) approved for usage in pediatric patients in the United States, it is used frequently in children worldwide. The development of receptor specific drugs is a growing industry and studies such as this demonstrate the potential benefits of these drugs. Unfortunately, what is frequently missing from these studies is any pharmacokinetic data which is essential for determining safety and efficacy of these drugs in pediatric patients. This type of information will be necessary to further expand the roles of tramadol in clinical practice.

Reviewed by: Jeffrey L. Galinkin, MD, Children's Hospital, Philadelphia, PA


Balanced analgesia in the perioperative period: Is there a place for Ketamine?

M De Kock, P Lavand'homme, H Waterloos. Pain 2001; 92:373-380.

Review: In a randomized, double-blinded, controlled study, the authors investigated the preemptive analgesic effect of "subanesthetic" doses of ketamine in 100 adult patients undergoing rectal adenocarcinoma surgery under combined general and epidural anesthesia. All patients received continuous infusions of propofol and alfentanil as well as epidural bupivacaine, sufentanil and clonidine. Patients were randomized to receive no ketamine
(Group 1); IV ketamine 0.25 mg/kg followed by an infusion of 0.125 mg/kg/hr (Group 2); IV ketamine 0.5 mg/kg followed by an infusion of 0.25 mg/kg/hr (Group 3); epidural ketamine 0.25 mg/kg followed by an infusion of 0.125 mg/kg/hr (Group 4); epidural ketamine 0.5 mg/kg followed by an infusion of 0.25 mg/kg/hr (Group 5). Group 3 demonstrated significantly less wound hyperalgesia, received less PCA morphine in the posoperative period, and reported less chronic postoperative pain through the sixth postoperative month.

Comment: This well-designed study compared the preemptive analgesic effect of IV and epidural ketamine in patients receiving combined general and epidural anesthesia. Subanesthetic doses of ketamine were administered to avoid postoperative dissociative effects of ketamine. All patients received balanced epidural anesthesia consisting of bupivacaine, sufentanil and clonidine. Interestingly, only patients receiving the higher dose of IV ketamine demonstrated a preemptive analgesic effect. The authors postulated that the absence of any demonstrable benefit from epidural ketamine - which is inconsistent with other reports _ was due to the epidural administration of bupivacaine, sufentanil, and clonidine. Epidural balockade may have prevented blockade of NMDA receptors since receptor channels must be in the open state to enable ketamine binding. Furthermore, the preemptive effect of IV ketamine suggests a "more central site for the anti-hyperalgesic actions of ketamine." The authors note that ketamine produces analgesia not only by blockade of NMDA receptors but also by monoaminergic descending inhibitory system activation and by peripheral inhibition of proinflammatory cytokines. Subanesthetic doses of ketamine appear to produce a preemptive analgesic effect and may be a useful adjuvant for perioperative balanced analgesia. The mechanism and optimum route of administration remain uncertain.

Reviewed by: John T. Algren, MD, Vanderbilt Children's Hospital, Nashville, TN


An audit of perioperative management of autistic children

Van Der Walt J.H. and Moran C., Paediatric Anaesthesia 2001 11:401-408

This descriptive article is a report of the largest collection of autistic children reported in the perioperative period. Since these children have significant idiosyncratic needs, every anesthesiologist should be familiar with the special requirements, which will enhance the positive outcome of this highly stressful situation. The audit revealed common practice patterns and the heterogeneity of some management issues. These children are best not to be kept waiting unnecessarily or should be allowed their individual preference of distraction. Premedication was not always used and each of the three patterns of premedication (p.o. midazolam, p.o. ketamine, or combination) all resulted in approximately the same success, however ketamine or the combination was reserved for the more severely affected children. Ketamine i.m. was necessary in a small number of children. Physical restraint was sometimes difficult in the child who received unsatisfactory premedication. Sevoflurane was used only for induction and interestingly the authors report no emergence delirium. I find this unexpected as this group of children is at higher risk of emergence phenomena since they have insufficiently developed cortical inhibitory responses. When possible, the authors recommend combining surgical procedures to limit the number of perioperative presentations and removal of intravenous catheters at the earliest possible time.

My personal experience with children with autism includes use of prehospital premedication, parent present induction and at emergence in PACU, and multimodal analgesia to minimize any contribution of pain to emergence behavioral disorders. The authors specifically do not advance their audit as a scientifically controlled trial. They are to be congratulated for assembling the records of care of these very challenging patients and providing insights into the limitations of usual practice of care. An optimal management strategy of management of children with autism is not offered here, however, commonsense, simple alterations from our usual hectic pace can significantly improve parent satisfaction with the perioperative experience for their child.

Reviewed by: Joseph R. Tobin, MD, Wake Forest University School of Medicine


Review of ethics in paediatric anaesthesia: research issues

Edgar J, Morton N.S., and Pace N.A., Paediatric Anaesthesia 2001 11:473-477

This review article is one of a three part series. The first review examined issues of consent for participation of children in research trials and the final issue in the series will examine issues in paediatric intensive care and organ donation and transplantation. The authors review one basic concept of therapeutic and nontherapeutic (of no direct benefit to the participant) research and the ethical tolerability of risks associated with research when the child may not directly benefit from the research. They further present issues of assent and parental consent. They make an issue of no lower age limit for the child to assent, but this is not practical, as many children whom we intend as research participants could not understand issues involved in the research to give informed consent. I hope that the authors are not implying that research should not be performed on the youngest patients as this would prolong the off label use of new pharmaceuticals which is paradoxical to the recent strides for which we have advocated. The authors do iterate that consent should be an active, not passive or implied process with an opportunity to opt out of participation.

The manuscript does refer to issues of confidentiality, which can cause a `Catch-22' situation. For example, if a postmenarchal female may be enrolled, but pregnancy is an exclusion criterion, then a pregnancy test should be performed. However, should the result be positive, the investigator may be confined by confidentiality to give this information only to the patient, not the parent and the child will be excluded from participation. Each of the above issues deserves even further discussion for all of us who may participate in clinical trials in a more extensive review.

Incongruent with the title of the manuscript, the authors then delve into issues regarding clinical care of the male child for circumcision and the child of the Jehovah's witness faith. Ethical issues regarding the clinical care of these children are discussed, but these are unrelated to research issues. Again, important points are brought to discussion but insufficient space is available for a more comprehensive discussion of relevant issues. These sections would be better suited for a different manuscript. Although I enjoyed this article, it does not sufficiently discuss core ethical issues in research involving infants and children. Editors of our many journals should be sensitive to the investigators' and readers' thirst for improving the quality and impact of pediatric research in our field along with other pediatric subspecialties.

Reviewed by: Joseph R. Tobin, MD, Wake Forest University School of Medicine #include ./footer_include.iphtml