Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta-analytic and meta-regression approach.

BACKGROUND: Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta-analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients. METHOD: We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results. RESULTS: We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance. CONCLUSIONS: The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.

Neuromuscular-blocking agents for tracheal intubation in pediatric patients (0-12 years): A systematic review and meta-analysis.

BACKGROUND: The benefit of using neuromuscular-blocking agents to facilitate tracheal intubation in pediatric patients remains unclear due to variations in design, treatments, and results among trials. By combining the available evidence, we aimed to establish whether scientific findings are consistent and can be generalized across various populations, settings, and treatments. METHODS: A systematic search for randomized controlled trials, related to the use of neuromuscular-blocking agents for tracheal intubation in American Society of Anesthesiologists class I-II participants (0-12 years), was performed. We considered all randomized controlled trials that studied whether intubation conditions and hemodynamics obtained by using neuromuscular-blocking agents were equivalent to those that were achieved without neuromuscular-blocking agents. We combined the outcomes in Review Manager 5.3 (RevMan, The Cochrane Collaboration) by pairwise random-effects meta-analysis using a risk ratio (RR) for intubation conditions and mean difference for hemodynamic values (mean [95% Confidence Intervals]). Heterogeneity among trials was explored using sensitivity analyses. RESULTS: We identified 22 eligible randomized controlled trials with 1651 participants. Overall, the use of a neuromuscular-blocking agent was associated with a clinically important increase in the likelihood of both excellent (RR = 1.41 [1.19-1.68], I2  = 76%) and acceptable (RR = 1.13 [1.07-1.19], I2  = 68%) intubating conditions. There is strong evidence that both unacceptable intubation conditions (RR = 0.35 [0.22-0.46], I2  = 23%) and failed first intubation attempts (RR = 0.25 [0.14-0.42], I2  = 0%) were less likely to occur when a neuromuscular-blocking agent was used compared with when it was not. Higher systolic or mean arterial pressures (mean difference = 13.3 [9.1-17.5] mm Hg, I2  = 69%) and heart rates (mean difference = 15.9 [11.0-20.8] beats/min, I2  = 75%) as well as a lower incidence of arrhythmias were observed when tracheal intubation was facilitated by neuromuscular-blocking agents. CONCLUSION: The use of a neuromuscular-blocking agent during light-to-moderate depth of anesthesia can improve the quality as well as the success rate of tracheal intubation and is associated with better hemodynamic stability during induction of anesthesia.

Evaluation of anesthesia in endoscopic strip craniectomy: A review of 121 patients.

OBJECTIVE: The aim of this study was to evaluate pre-, intra-, and postoperative anesthetic parameters in endoscopic strip craniectomy in order to improve anesthesiological care. MATERIALS AND METHODS: This is a retrospective patient cohort study of our first 121 patients treated by endoscopic strip craniectomy. Preoperative as well as intra- and postoperative anesthesiological and neurological parameters were analyzed. Furthermore, the need for intensive care unit admission, blood loss, and blood transfusion rate were measured. RESULTS: The mean age of patients was 3.9 months (standard deviation = 1) at a mean weight of 6.3 kg (standard deviation = 1.3). Comorbidity was registered in 13 (11%) patients of which 5 had syndrome-related comorbidities. Mean duration of anesthesia was 131 minutes (standard deviation = 32) . One hundred and sixteen patients were induced by mask induction with sevoflurane and 5 patients were induced intravenously. In 10 patients, mild intraoperative hypothermia (between 35 and 36 degrees Celsius) occurred. The mean estimated blood loss was 35.4 mL (standard deviation = 28.9) and blood transfusion rate was 21.5%. Brief and small intraoperative oxygen saturation drops were common during this study. No indication for venous air embolism was found based on endtidal CO2 . Postoperative temperature above 38 degrees Celsius occurred 16 times and benign deviations in postoperative cardiopulmonary parameters occurred in 17 patients. Postoperative pain management was mainly established by paracetamol and low-dose morphine when necessary. No postoperative neurological symptoms were reported and no deaths occurred. CONCLUSION: These patients had a relatively short intraoperative course with stable vital parameters during surgery. We report a low incidence of significant venous air embolism, a blood transfusion rate of 21% and only minor perioperative disturbances in vital parameters.

Endoscopically assisted craniosynostosis surgery (EACS): The craniofacial team Nijmegen experience.

INTRODUCTION: An evaluation of our first 111 consecutive cases of non-syndromic endoscopically assisted craniosynostosis surgery (EACS) followed by helmet therapy. METHODS: Retrospective analysis of a prospective registration database was performed. Age, duration of surgery, length of hospital stay, blood loss, transfusion rate, cephalic index and duration of helmet therapy were evaluated. An online questionnaire was used to evaluate the burden of the helmet therapy for the child and parents. RESULTS: 111 EAC procedures were performed: 64 for scaphocephaly, 34 for trigonocephaly and13 for anterior plagiocephaly. The mean age at the time of surgery was 3.9 (±1) months, mean surgical time was 58 (±18) minutes, mean blood loss was 34 (±28) ml, transfusion rate was 22% (n = 26), mean duration of postoperative helmet therapy was 10 (±2.5) months, mean preoperative and postoperative CI were respectively 0.67(±0.057) and 0.72 (±0.062) in scaphocephalic patients and the mean length of hospital stay was 2.6 (±1) days. The burden of the helmet therapy for the child and his family was deemed very low. CONCLUSION: EACS for non-syndromic patients shows low morbidity rates, short surgical time, short length of hospital stay, little blood loss and low need for blood transfusion and is associated with satisfying cosmetic results.

The effect of pregabalin and s-ketamine in total knee arthroplasty patients: A randomized trial.

BACKGROUND AND AIMS: Pain reduction is important for rehabilitation after total knee arthroplasty. Intra- and peri-articular infiltration with local anesthetics may be an alternative to commonly used locoregional techniques. Adding pregabalin orally and s-ketamine intravenously may further reduce postoperative pain. MATERIAL AND METHODS: This prospective, randomized, double-blind, placebo-controlled study compared two methods of perioperative analgesia. Control patients received a standardized multimodal postoperative analgesic regime of paracetamol, diclofenac, and piritramide-patient-controlled analgesia, including ropivacaine knee infiltration during surgery. The study group received pregabalin orally and s-ketamine intravenously as an additional medication to the standard multimodal regimen. The control group received placebo. RESULTS: The study group showed lower piritramide consumption during the first 24 h (P: 0.043), but with more side effects such as diplopia and dizziness. CONCLUSION: Addition of pregabalin and s-ketamine resulted in lower piritramide consumption during the first 24 h postoperatively. However, more investigation on benefits versus side effects of this medication is required.

Increased mitochondrial ATP production capacity in brain of healthy mice and a mouse model of isolated complex I deficiency after isoflurane anesthesia.

We reported before that the minimal alveolar concentration (MAC) of isoflurane is decreased in complex I-deficient mice lacking the NDUFS4 subunit of the respiratory chain (RC) (1.55 and 0.81% at postnatal (PN) 22-25 days and 1.68 and 0.65% at PN 31-34 days for wildtype (WT) and CI-deficient KO, respectively). A more severe respiratory depression was caused by 1.0 MAC isoflurane in KO mice (respiratory rate values of 86 and 45 at PN 22-25 days and 69 and 29 at PN 31-34 days for anesthetized WT and KO, respectively). Here, we address the idea that isoflurane anesthesia causes a much larger decrease in brain mitochondrial ATP production in KO mice thus explaining their increased sensitivity to this anesthetic. Brains from WT and KO mice of the above study were removed immediately after MAC determination at PN 31-34 days and a mitochondria-enriched fraction was prepared. Aliquots were used for measurement of maximal ATP production in the presence of pyruvate, malate, ADP and creatine and, after freeze-thawing, the maximal activity of the individual RC complexes in the presence of complex-specific substrates. CI activity was dramatically decreased in KO, whereas ATP production was decreased by only 26% (p < 0.05). The activities of CII, CIII, and CIV were the same for WT and KO. Isoflurane anesthesia decreased the activity of CI by 30% (p < 0.001) in WT. In sharp contrast, it increased the activity of CII by 37% (p < 0.001) and 50% (p < 0.001) and that of CIII by 37% (p < 0.001) and 40% (p < 0.001) in WT and KO, respectively, whereas it tended to increase that of CIV in both WT and KO. Isoflurane anesthesia increased ATP production by 52 and 69% in WT (p < 0.05) and KO (p < 0.01), respectively. Together these findings indicate that isoflurane anesthesia interferes positively rather than negatively with the ability of CI-deficient mice brain mitochondria to convert their main substrate pyruvate into ATP.

Isoflurane anesthetic hypersensitivity and progressive respiratory depression in a mouse model with isolated mitochondrial complex I deficiency.

BACKGROUND: Children with mitochondrial disorders are frequently anesthetized for a wide range of operations. These disorders may interfere with the response to surgery and anesthesia. We examined anesthetic sensitivity to and respiratory effects of isoflurane in the Ndufs4 knockout (KO) mouse model. These mice exhibit an isolated mitochondrial complex I (CI) deficiency of the respiratory chain, and they also display clinical signs and symptoms resembling those of patients with mitochondrial CI disease. METHODS: We investigated seven Ndufs4(-/-) knockout (KO), five Ndufs4(+/-) heterozygous (HZ) and five Ndufs4(+/+) wild type (WT) mice between 22 and 25 days and again between 31 and 34 days post-natal. Animals were placed inside an airtight box, breathing spontaneously while isoflurane was administered in increasing concentrations. Minimum alveolar concentration (MAC) was determined with the bracketing study design, using the response to electrical stimulation to the hind paw. RESULTS: MAC for isoflurane was significantly lower in KO mice than in HZ and WT mice: 0.81% ± 0.01 vs 1.55 ± 0.05% and 1.55 ± 0.13%, respectively, at 22-25 days, and 0.65 ± 0.05%, 1.65 ± 0.08% and 1.68 ± 0.08% at 31-34 days. The KO mice showed severe respiratory depression at lower isoflurane concentrations than the WT and HZ mice. CONCLUSION: We observed an increased isoflurane anesthetic sensitivity and severe respiratory depression in the KO mice. The respiratory depression during anesthesia was strongly progressive with age. Since the pathophysiological consequences from complex I deficiency are mainly reflected in the central nervous system and our mouse model involves progressive encephalopathy, further investigation of isoflurane effects on brain mitochondrial function is warranted.

General anaesthesia in an adult patient with Morquio syndrom with emphasis on airway issues.

Patients with Morquio syndrome possess a number of characteristics which may complicate an anaesthetic procedure. The most important is that a deposition of mucopolysaccharides in the soft tissues of the oro-pharynx distorts the airway, making the airway management difficult, while the atlanto-axial instability puts these patients at risk of subluxation and quadriparesis. As the endotracheal intubation in Morquio syndrome patients may be difficult or even impossible, we recommend the technique of awake fiberoptic intubation to be considered. Our approach to awake fiberoptic intubation in an adult patient is described in this case report.

Reversal of rocuronium-induced neuromuscular block by sugammadex is independent of renal perfusion in anesthetized cats.

PURPOSE: Sugammadex is a selective relaxant binding agent designed to encapsulate the aminosteroidal neuromuscular blocking agent rocuronium, thereby reversing its effect. Both sugammadex and the sugammadex-rocuronium complex are eliminated by the kidneys. This study investigated the effect of sugammadex on recovery of rocuronium-induced neuromuscular block in cats with clamped renal pedicles, as a model for acute renal failure. METHODS: Twelve male cats were divided into two groups and anesthetized with medetomidine, ketamine, and alpha-chloralose. The cats were intubated and ventilated with a mixture of oxygen and air. Neuromuscular monitoring was performed by single twitch monitoring. Rocuronium 0.5 mg/kg i.v. was administered. After spontaneous recovery from neuromuscular block, both renal pedicles were ligated. A second dose of rocuronium 0.5 mg/kg i.v. was given. One minute after disappearance of the twitches, in Group 1 placebo (0.9% saline) and in Group 2 sugammadex 5.0 mg/kg i.v. was administered. Onset time, duration of neuromuscular block, and time to recovery to 25, 50, 75, and 90% were determined. RESULTS: After renal pedicle ligation, sugammadex reversed rocuronium-induced neuromuscular block significantly faster than spontaneous recovery. Mean time (SEM) to 90% recovery of the twitch response was 4.7 (0.25) min (Group 2) versus 31.1 (5.0) min (Group 1) (p < 0.0001). No signs of recurrence of neuromuscular block were observed for 90 min after complete twitch restoration. Sugammadex caused no significant cardiovascular effects. CONCLUSION: Sugammadex rapidly and effectively reversed rocuronium-induced neuromuscular block in anesthetized cats, even when both renal pedicles were ligated and renal elimination of the drugs was no longer possible.

Sugammadex reverses neuromuscular block induced by 3-desacetyl-vecuronium, an active metabolite of vecuronium, in the anaesthetised rhesus monkey.

BACKGROUND AND OBJECTIVE: 3-Desacetyl-vecuronium is an active metabolite of the neuromuscular blocking agent (NMBA) vecuronium, which might lead to residual paralysis after prolonged administration of vecuronium in critically ill patients with renal failure. This study investigated the ability of sugammadex to reverse 3-desacetyl-vecuronium-induced neuromuscular block (NMB) in the anaesthetised rhesus monkey. METHODS: Experiments were performed in anaesthetised female rhesus monkeys. After bolus intravenous injection of vecuronium (n = 8) or 3-desacetyl-vecuronium (n = 8) 10 µg kg(-1) (ED90), a continuous infusion of the same NMBA was started to maintain the first twitch of the train-of-four (TOF) at 10% of baseline value. The infusion was stopped and NMB recovered spontaneously. The procedure was repeated, but immediately after stopping the infusion, an intravenous bolus dose of sugammadex 0.5 or 1.0 mg kg(-1) was given. For each NMBA, four placebo experiments were performed, in which the second recovery from NMB was also spontaneous. For all experiments, time to recovery of the TOF ratio to 90% was retrieved. RESULTS: After administration of sugammadex for reversal of 3-desacetyl-vecuronium-induced NMB, recovery was significantly faster than spontaneous recovery. Mean time to recovery of TOF to 90% was 3.2 min (sugammadex 0.5 mg kg(-1)) and 2.6 min (1.0 mg kg(-1)), compared to spontaneous recovery (17.6 min). For vecuronium-induced NMB, mean time to recovery of TOF to 90% was 17.1 min (0.5 mg kg(-1)) and 4.6 min (1.0 mg kg(-1)), compared to spontaneous recovery (23.4 min). CONCLUSION: Sugammadex rapidly and effectively reversed 3-desacetyl-vecuronium-induced NMB in the rhesus monkey, at a lower dose than that needed to reverse vecuronium-induced NMB.

Longer than expected-duration of caudal analgesia with two different doses of levobupivacaine in children undergoing hypospadias repair.

OBJECTIVE: To assess our study design and to obtain preliminary data for a dose-effect study on levobupivacaine for caudal analgesia in patients undergoing hypospadias repair. STUDY DESIGN: non randomised, non-blinded pilot study. METHOD: For this non-randomized, non-blinded pilot study, 20 patients (median age 17 months, median weight 10.5 kg) were allocated to two groups receiving either 0.5 mL kg(-1) levobupivacaine 0.125% (Group 0) or 0.5 mL kg(-1) levobupivacaine 0.375% (Group 1) caudally after induction of anaesthesia for pain control. No further analgesia was given before, during or after the procedure. Pain scores (Children's and Infants' Postoperative Pain Scale) were recorded throughout the observation period, which lasted from the start of the procedure until hospital discharge on the following day. RESULTS: Group 0: six out of 10 patients remained pain free throughout the observation period. Group 1: six out of seven patients remained pain free throughout the observation period. CONCLUSION: Both concentrations of levobupivacaine provided excellent analgesia throughout surgery. The postoperative analgesia with both doses of levobupivacaine was found to be significantly longer lasting than previously reported. The study design, with a tight and extensive observation scheme, proved to be feasible, but given the surprisingly long-lasting analgesia, the observation period needs to be extended in future studies.

Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and efficient recovery from profound neuromuscular block was achieved, and no adverse events or other safety concerns were observed.

Stuve Wiedemann syndrome and related syndromes: case report and possible anesthetic complications.

Stuve Wiedemann syndrome (SWS) is an autosomal recessively inherited syndrome which is characterized by bowing of the long bones, camptodactyly, facial dysmorphism, hypotonia, feeding and swallowing difficulties, and respiratory distress. In most cases episodes of unexplained hyperthermia are present. Patients with SWS can develop hyperthermia in conjunction with anesthesia and surgery, and a relationship has been suggested between the syndrome and malignant hyperthermia. We describe a 3-year-old child diagnosed with SWS to whom we administered general anesthesia during the removal of a corneal ulcer and dilatation of the lacrimal duct. Our patient had received, uncomplicated, inhalational anesthesia five times previously for different operations. There were no anesthesia-related complications in the present or previous perioperative periods. On one occasion the patient developed mild postoperative hyperthermia. We believe that this hyperthermia is different from the specific disorder of malignant hyperthermia and that sevoflurane can be safely used in patients with SWS. We also describe symptomatically related syndromes and their theoretical risks for anesthesia.

Neuromuscular and mitochondrial disorders: what is relevant to the anaesthesiologist?

PURPOSE OF REVIEW: The review provides an up-to-date information to the anaesthesiologist about the more frequent and important neuromuscular disorders for which new basic insights or clinical implications have been reported. RECENT FINDINGS: The findings include the mechanisms of the hyperkalemia after succinylcholine in patients with upregulation of acetylcholine receptors. New insights into the mechanism of malignant hyperthermia-like reactions such as rhabdomyolysis during anaesthesia in patients with Duchenne muscular dystrophy have been published. The importance of mitochondrial defects and the effect of agents used in anaesthesia on mitochondrial function are also highlighted. SUMMARY: The increased understanding of the genetics and pathophysiology of common muscle disorders may lead to a decrease in life-threatening complications related to surgery and anaesthesia. However, there is still a lack of prospective clinical studies to determine which is the safest anaesthetic technique for these patients.

Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study.

BACKGROUND: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients. METHODS: Forty-five American Society of Anesthesiologists physical status I and II patients (aged 18-64 yr) scheduled to undergo surgical procedures (anticipated anesthesia duration >/= 90 min) were randomly assigned to a phase II, multicenter, assessor-blinded, placebo-controlled, parallel, dose-finding study. Anesthesia was induced and maintained with propofol and an opioid. Profound neuromuscular blockade was induced with 1.2 mg/kg rocuronium bromide. Sugammadex (2.0, 4.0, 8.0, 12.0, or 16.0 mg/kg) or placebo (0.9% saline) was then administered 5 min after the administration of rocuronium. Neuromuscular function was monitored by acceleromyography, using train-of-four nerve stimulation. Recovery time was the time from the start of administration of sugammadex or placebo, to recovery of the train-of-four ratio to 0.9. Safety assessments were performed on the day of the operation and during the postoperative and follow-up period. RESULTS: A total of 43 patients received either sugammadex or placebo. Increasing doses of sugammadex reduced the mean recovery time from 122 min (spontaneous recovery) to less than 2 min in a dose-dependent manner. Signs of recurrence of blockade were not observed. No serious adverse events related to sugammadex were reported. Two adverse events possibly related to sugammadex were reported in two patients (diarrhea and light anesthesia); however, both patients recovered without sequelae. CONCLUSIONS: Sugammadex rapidly and effectively reversed profound rocuronium-induced neuromuscular blockade in humans and was well tolerated.

Anesthesia-related morbidity and mortality after surgery for muscle biopsy in children with mitochondrial defects.

BACKGROUND: Children with mitochondrial defects (MD) may have an increased risk for cardiorespiratory and neurological complications from anesthesia. The aim of this study was to determine the incidence of perioperative complications and adverse events in children with MD. METHODS: We performed a retrospective review of the anesthesia, surgical and medical records of 155 children up to 10 years who underwent a diagnostic surgical muscle biopsy for suspected mitochondrial and muscle disorders between 1999 and 2003. The data of the 122 patients where a definite MD diagnosis was found were analyzed. Anesthesia was conducted according to the discretion of the attending staff. In children with MD the activity of the different complexes of the oxidative phosphorylation system was measured. RESULTS: From the preoperative assessment, signs of encephalopathy were most frequent (n = 93), followed by muscle weakness (n = 32), lactic acidosis (n = 15), cardiomyopathy and/or conduction defects (n = 10) and chronic respiratory problems (n = 7). The mean age of the children with MD was 32.4 months (SD = 26.9). The mean duration of anesthesia was 36.0 min (SD = 12.6) and the mean length of stay in the recovery room was 33.0 min (SD = 24.0). There were no major changes in heart rate or blood pressure which required pharmacological intervention during anesthesia or postanesthesia care unit (PACU) stay. A short episode of SpO2 <80% with airway obstruction occurred once in the PACU. Biochemical analysis in the children with a MD showed an isolated deficiency of one of the five protein complexes of oxidative phosphorylation in 42 children, a combination of complex deficiencies in 41 and no definite localization in 39 children. CONCLUSION: With standard preoperative assessment, monitoring and anesthesia management, there were no major peroperative and postoperative anesthesia-related complications in children undergoing surgical muscle biopsy with a MD diagnosis.