Peter Szmuk

Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial

__Background__ In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes. __Methods__ In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks’ postmenstrual age who were born at more than 26 weeks’ gestation and were undergoing inguinal herniorrhaphy, without previous exposure to general anaesthesia or risk factors for neurological injury. Patients were randomly assigned (1:1) by use of a web-based randomisation service to receive either awake-regional anaesthetic or sevoflurane-based general anaesthetic. Anaesthetists were aware of group allocation, but individuals administering the neurodevelopmental assessments were not. Parents were informed of their infants group allocation upon request, but were told to mask this information from assessors. The primary outcome measure was full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III), at 5 years of age. The primary analysis was done on a per-protocol basis, adjusted for gestational age at birth and country, with multiple imputation used to account for missing data. An intention-totreat analysis was also done. A difference in means of 5 points was predefined as the clinical equivalence margin. This completed trial is registered with ANZCTR, number ACTRN12606000441516, and ClinicalTrials.gov, number NCT00756600. __Findings__ Between Feb 9, 2007, and Jan 31, 2013, 4023 infants were screened and 722 were randomly allocated: 363 (50%) to the awake-regional anaesthesia group and 359 (50%) to the general anaesthesia group. There were 74 protocol violations in the awake-regional anaesthesia group and two in the general anaesthesia group. Primary outcome data for the per-protocol analysis were obtained from 205 children in the awake-regional anaesthesia group and 242 in the general anaesthesia group. The median duration of general anaesthesia was 54 min (IQR 41–70). The mean FSIQ score was 99·08 (SD 18·35) in the awake-regional anaesthesia group and 98·97 (19·66) in the general anaesthesia group, with a difference in means (awake-regional anaesthesia minus general anaesthesia) of 0·23 (95% CI –2·59 to 3·06), providing strong evidence of equivalence. The results of the intention-to-treat analysis were similar to those of the per-protocol analysis. __Interpretation__ Slightly less than 1 h of general anaesthesia in early infancy does not alter neurodevelopmental outcome at age 5 years compared with awake-regional anaesthesia in a predominantly male study population.Summary Background There is pre-clinical evidence that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia may have an increased risk of poorer neurodevelopmental outcome. This trial aims to determine if GA in infancy has any impact on neurodevelopmental outcome. The primary outcome for the trial is neurodevelopmental outcome at 5 years of age. The secondary outcome is neurodevelopmental outcome at two years of age and is reported here. Methods We performed an international assessor-masked randomised controlled equivalence trial in infants less than 60 weeks post-menstrual age, born at greater than 26 weeks gestational age having inguinal herniorrhaphy. Infants were excluded if they had existing risk factors for neurologic injury. Infants were randomly assigned to awake-regional (RA) or sevoflurane-based general anaesthesia (GA). Web-based randomisation was performed in blocks of two or four and stratified by site and gestational age at birth. The outcome for analysis was the composite cognitive score of the Bayley Scales of Infant and Toddler Development, Third Edition. The analysis was as-per-protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. The trial was registered at ANZCTR, ACTRN12606000441516 and ClinicalTrials.gov, NCT00756600. Findings Between February 2007, and January 2013, 363 infants were randomised to RA and 359 to GA. Outcome data were available for 238 in the RA and 294 in the GA arms. The median duration of anaesthesia in the GA arm was 54 minutes. For the cognitive composite score there was equivalence in means between arms (RA-GA: +0·169, 95% CI −2·30 to +2·64). Interpretation For this secondary outcome we found no evidence that just under an hour of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at two years of age compared to RA.

Prediction of difficult laryngoscopy in obese patients by ultrasound quantification of anterior neck soft tissue

In 50 morbidly obese patients, we quantified the soft tissue of the neck from the skin to the anterior aspect of the trachea at the vocal cords using ultrasound. Thyromental distance, mouth opening, limited neck mobility, modified Mallampati score, abnormal upper teeth, neck circumference and sleep apnoea were assessed as predictors of difficult laryngoscopy. Of the nine (18%) cases of difficult laryngoscopy, seven (78%) had a history of obstructive sleep apnoea, compared with two of the 41 patients (5%) in whom laryngoscopy was easy (p < 0.001). Patients in whom laryngoscopy was difficult had more pretracheal soft tissue (mean (SD) 28 (2.7) mm vs. 17.5 (1.8) mm; p < 0.001) and a greater neck circumference (50 (3.8) vs. 43.5 (2.2) cm; p < 0.001). None of the other predictors correlated with difficult laryngoscopy. We conclude that an abundance of pretracheal soft tissue at the level of the vocal cords is a good predictor of difficult laryngoscopy in obese patients.

Difficult airway management practice patterns among anesthesiologists practicing in the United States: have we made any progress?

STUDY OBJECTIVE To determine the extent instruction and practice in the use of airway devices and techniques varies among anesthesiologists practicing in the United States. DESIGN Survey questionnaire. SETTING University medical center. MEASUREMENTS Questionnaires were completed by American-trained anesthesiologists who attended the 1999 American Society of Anesthesiologists (ASA) Annual Meeting. Data collected included demographics, education, skills with airway devices/techniques, management of clinical difficult airway scenarios, and the use of the ASA Difficult Airway Algorithm. MAIN RESULTS 1) DEMOGRAPHICS: 452 questionnaires were correctly completed; 62% attending anesthesiologists, 70% <50 years, 81% males, 44% from academic institutions, 63% >10 years of practice, 81% night duty, 77% board certified. 2) Education: 71% had at least one educational modality: difficult airway rotation, workshops, conferences, books, and simulators. 3) Skills: Miller blade 61%, Bullard laryngoscope 32%, LMA 86%, Combitube 43%, bougie 43%, exchangers 47%, cuffed oropharyngeal airway (COPA) 34%, retrograde 41%, transtracheal needle jet ventilation 34%, cricothyrotomy 21%, fiberoptics 59%, and blind nasal intubation 78%. The average reported use of special airway devices/techniques was 47.5%. 4) Management choices: failed intubation/ventilation: LMA (81%) and for all other situations: fiberoptic intubation. Use of ASA Difficult Airway Algorithm in clinical practice (86%). CONCLUSION Fiberoptic intubation and the LMA are most popular in management of the difficult airway.

The Accuracy of Electrocardiogram-Controlled Central Line Placement

BACKGROUND:Electrocardiogram (ECG) guidance to confirm accurate positioning of central venous catheters (CVC), placed before surgery in the operating room, is rarely used in the United States. We designed this randomized, controlled trial to investigate whether the use of this technique impacts the accuracy of CVC placement. METHODS:Patients in group ECG (n = 147) had a CVC placed using right-atrial ECG to guide catheter tip positioning. CVCs in group NO-ECG (n = 143) were positioned without this technique. RESULTS:Overall, guidewire-ECG control resulted in more correctly positioned CVCs (96% vs 76%, P ≤ 0.001) without increasing placement time. Significantly more CVCs were placed in the middle of the superior vena cava in group ECG (P ≤ 0.001), although placement into the right atrium or right ventricle and into other vessels occurred significantly more often in group NO-ECG (P ≤ 0.001). Twenty patients in group NO-ECG required repositioning of their CVC after surgery, whereas this maneuver was necessary only in three patients in group ECG (P ≤ 0.001). CONCLUSIONS:ECG guidance allows for more accurate CVC placement, and should be considered to increase patient safety and reduce costs associated with repositioning procedures.

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles

Pyloric stenosis is sometimes associated with hemodynamic instability and postoperative apnea. In this multicenter study we examined the hemodynamic response and recovery profile of remifentanil and compared it with that of halothane in infants undergoing pyloromyotomy. After atropine, propofol, and succinylcholine administration and tracheal intubation, patients were randomized (2:1 ratio) to receive either remifentanil with nitrous oxide and oxygen or halothane with nitrous oxide and oxygen as the maintenance anesthetic. Pre- and postoperative pneumograms were done and evaluated by an observer blinded to the study. Intraoperative hemodynamic data and postanesthesia care unit (PACU) discharge times, PACU recovery scores, pain medications, and adverse events (vomiting, bradycardia, dysrhythmia, and hypoxemia) were recorded by the study’s research nurse. There were no significant differences in patient age or weight between the two groups. There were no significant differences in hemodynamic values between the two groups at the various intraoperative stress points. The extubation times, PACU discharge times, pain medications, and adverse events were similar for both groups. No patient anesthetized with remifentanil who had a normal preoperative pneumogram had an abnormal postoperative pneumogram, whereas three patients with a normal preoperative pneumogram who were anesthetized with halothane had abnormal pneumograms after.

The Incidence of Class “zero” Airway and the Impact of Mallampati Score, Age, Sex, and Body Mass Index on Prediction of Laryngoscopy Grade

IMPLICATIONS In an earlier study we proposed the addition of a new airway class, zero (visualization of the epiglottis), to the four classes of the modified Mallampati classification. In this prospective study, 764 surgical patients were assessed with regard to their airway class (including class zero), laryngoscopy grade, and the effect of the airway class and other predictors on the laryngoscopy grade.

Antinociceptive and cardiovascular properties of esmolol following formalin injection in rats.

Purpose: To assess the role of esmolol, a β1 receptor blocker, in the modulation of pain in the absence of anesthesia.Methods: Rats were chronically instrumented to record mean arterial blood pressure (MAP) and heart rate (HR). Animals were divided into three groups. Group 1 [esmolol high (EH) 150 mg·kg−1·hr−1; n=9], Group 2 [esmolol low (EL) 40 mg·kg−1·hr−1; n=7] and Group 3 saline (n=9). Formalin 5% was injected in the rat hind paw. Formalin-induced lifting, MAP and HR were recorded at five minute intervals for 35 min after formalin injection.Results: Formalin was associated with an early (Phase 1; 0–5 min) and late nociceptive response (Phase 2; 10–35 min). Esmolol did not affect Phase 1. Although low dose esmolol had minimum effects on nociceptive Phase 2, it was diminished with high dose esmolol. Formalin induced biphasic increases in MAP and HR. Although esmolol did not affect the initial increase in MAP, high dose esmolol blunted the secondary increase in MAP. Both low and high doses of esmolol inhibited formalin-induced tachycardia during the first 30 min.Conclusion: Our data suggest that esmolol leads to analgesia and reduction of cardiovascular responses to pain.RésuméObjectif: Cette étude a été réalisée pour étudier le rôle de l’esmolol, un bloqueur des récepteurs béta 1 dans la modulation de la douleur en l’absence d’anesthésie.Méthode: Des rats ont été instrumentés pour enregistrer la tension artérielle moyenne (TAM), et la fréquence cardiaque (FC). Les animaux ont été divisés en 3 groupes. Le groupe 1 [esmolol à la dose de 150 µg·kg−1·hr−1; n=9], le groupe 2 [esmolol à la dose de 40 µg·kg−1·hr−1; n=7] et le groupe 3 [chlorure de sodium isotonique; n=9]. Le formol (5%) a été injecté par voie sous-cutanée dans la patte du rat. Les mouvements de la patte ainsi que la TAM et la FC ont été enregistrés à 5 min d’intervalles pendant 35 min après l’injection du formol.Résultats: L’activité physique qui accompagnait l’administration de formol a été représentée par une phase immédiate (Phase 1; 0–5 min) et une phase secondaire (Phase 2; 10–35 min). L’esmolol n’a pas produit d’effets significatifs sur les mouvements de la patte en Phase 1. Alors qu’à faible dose, l’esmolol n’a provoqué que peu d’effets sur les mouvements de la patte en Phase 2, à forte dose il a engendré une réponse significative. Le formol a produit des augmentations significatives de la TAM et de la FC. Bien que l’esmolol, à forte dose, n’a pas produit de changements significatifs sur la TAM, il a fortement diminué l’augmentation secondaire de la TAM. Les 2 doses d’esmolol ont diminué la tachycardie provoquée par l’injection de formol.Conclusion: Nos résultats suggèrent que l’administration d’esmolol s’associe à une diminution de l’hyperactivité liée à l’injection de formol dans la patte.

Peripartum general anaesthesia without tracheal intubation: incidence of aspiration pneumonia*

This study estimated the incidence of pulmonary aspiration during general anasthesia for obstetric procedures performed in the peripartum period (Caesarean sections were not studied). The records of 1870 patients anasthetised without tracheal intubation were reviewed retrospectively. The diagnosis of aspiration was based on the anasthetists written remarks and the postoperative course. Eighty per cent of patients received ketamine and a benzodiazepine, and the remaining 20% received methohexital or thiopental and fentanyl. No cricoid pressure or tracheal intubation was performed. A single case of mild aspiration was detected in a woman anasthetised with methohexital (an incidence of 0.053%). These results suggest that the risk of aspiration during general anasthesia without tracheal intubation, during and immediately after delivery, may not be higher in obstetric patients in the peripartum period, as has been reported previously.

Airway management complications in children with difficult tracheal intubation from the Pediatric Difficult Intubation (PeDI) registry: a prospective cohort analysis

BACKGROUND Despite the established vulnerability of children during airway management, remarkably little is known about complications in children with difficult tracheal intubation. To address this concern, we developed a multicentre registry (Pediatric Difficult Intubation [PeDI]) to characterise risk factors for difficult tracheal intubation, establish the success rates of various tracheal intubation techniques, catalogue the complications of children with difficult tracheal intubation, and establish the effect of more than two tracheal intubation attempts on complications. METHODS The PeDI registry consists of prospectively collected tracheal intubation data from 13 childrens hospitals in the USA. We established standard data collection methods before implementing the secure web-based registry. After establishing standard definitions, we collected and analysed patient, clinician, and practice data and tracheal intubation outcomes. We categorised complications as severe or non-severe. FINDINGS Between August, 2012, and January, 2015, 1018 difficult paediatric tracheal intubation encounters were done. The most frequently attempted first tracheal intubation techniques were direct laryngoscopy (n=461, 46%), fibre-optic bronchoscopy (n=284 [28%]), and indirect video laryngoscopy (n=183 [18%]) with first attempt success rates of 16 (3%) of 461 with direct laryngoscopy, 153 (54%) of 284 with fibre-optic bronchoscopy, and 101 (55%) of 183 with indirect video laryngoscopy. Tracheal intubation failed in 19 (2%) of cases. 204 (20%) children had at least one complication; 30 (3%) of these were severe and 192 (19%) were non-severe. The most common severe complication was cardiac arrest, which occurred in 15 (2%) patients. The occurrence of complications was associated with more than two tracheal intubation attempts, a weight of less than 10 kg, short thyromental distance, and three direct laryngoscopy attempts before an indirect technique. Temporary hypoxaemia was the most frequent non-severe complication. INTERPRETATION More than two direct laryngoscopy attempts in children with difficult tracheal intubation are associated with a high failure rate and an increased incidence of severe complications. These results suggest that limiting the number of direct laryngoscopy attempts and quickly transitioning to an indirect technique when direct laryngoscopy fails would enhance patient safety. FUNDING None.

Drug-induced sleep endoscopy for upper airway evaluation in children with obstructive sleep apnea†‡

To evaluate sites and characteristics of upper airway obstruction, as detected with drug‐induced sleep endoscopy (DISE) in children with obstructive sleep apnea (OSA).