Efficacy of different routes of acetaminophen administration for postoperative pain in children: a systematic review and network meta-analysis.

PURPOSE: Acetaminophen is the most common drug used to treat acute pain in the pediatric population, given its wide safety margin, low cost, and multiple routes for administration. We sought to determine the most efficacious route of acetaminophen administration for postoperative acute pain relief in the pediatric surgical population. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) that included children aged between 30 days and 17 yr who underwent any type of surgical procedure and that evaluated the analgesic efficacy of different routes of administration of acetaminophen for the treatment of postoperative pain. We searched MEDLINE, CENTRAL, Embase, CINAHL, LILACs, and Google Scholar databases for trials published from inception to 16 April 2023. We assessed the risk of bias in the included studies using the Cochrane Risk of Bias 1.0 tool. We performed a frequentist network meta-analysis using a random-effects model. Our primary outcome was postoperative pain using validated pain scales. RESULTS: We screened 2,344 studies and included 14 trials with 829 participants in the analysis. We conducted a network meta-analysis for the period from zero to two hours, including six trials with 496 participants. There was no evidence of differences between intravenous vs rectal routes of administration of acetaminophen (difference in means, -0.28; 95% confidence interval [CI], -0.62 to 0.06; very low certainty of the evidence) and intravenous vs oral acetaminophen (difference in means, -0.60; 95% CI, -1.20 to 0.01; low certainty of the evidence). For the comparison of oral vs rectal routes, we found evidence favouring the oral route (difference in means, -0.88; 95% CI, -1.44 to -0.31; low certainty of the evidence). Few trials reported secondary outcomes of interest; when comparing the oral and rectal routes in the incidence of nausea and vomiting, there was no evidence of differences (relative risk, 1.20; 95% CI, 0.81 to 1.78). CONCLUSION: The available evidence on the effect of the administration route of acetaminophen on postoperative pain in children is very uncertain. The outcomes of postoperative pain control and postoperative vomiting may differ very little between the oral and rectal route. Better designed and executed RCTs are required to address this important clinical question. STUDY REGISTRATION: PROSPERO (CRD42021286495); first submitted 19 November 2021.

RéSUMé: OBJECTIF: Compte tenu de sa large marge de sécurité, de son faible coût et de ses multiples voies d'administration, l'acétaminophène est le médicament le plus couramment utilisé pour traiter la douleur aiguë dans la population pédiatrique. Nous avons cherché à déterminer la voie d'administration d'acétaminophène la plus efficace pour le soulagement de la douleur aiguë postopératoire dans la population chirurgicale pédiatrique. MéTHODE: Nous avons réalisé une revue systématique d'études randomisées contrôlées (ERC) qui ont inclus des enfants âgé·es de 30 jours à 17 ans ayant bénéficié de n'importe quel type d'intervention chirurgicale et qui ont évalué l'efficacité analgésique de différentes voies d'administration d'acétaminophène pour le traitement de la douleur postopératoire. Nous avons mené des recherches dans les bases de données MEDLINE, CENTRAL, Embase, CINAHL, LILAC et Google Scholar pour en tirer les études publiées depuis leur création jusqu'au 16 avril 2023. Le risque de biais dans les études incluses a été évalué à l'aide de l'outil de Risque de biais 1.0 de Cochrane. Nous avons réalisé une méta-analyse de réseau fréquentiste à l'aide d'un modèle à effets aléatoires. Notre critère d'évaluation principal était la douleur postopératoire mesurée à l'aide d'échelles de douleur validées. RéSULTATS: Nous avons passé en revue 2344 études et inclus 14 études incluant un total de 829 enfants dans l'analyse. Nous avons mené une méta-analyse en réseau pour une période allant de zéro à deux heures, comprenant six études avec 496 participant·es. Il n'y avait aucune preuve de différences entre les voies d'administraion intraveineuse vs rectale de l'acétaminophène (différence de moyennes, −0,28; intervalle de confiance [IC] à 95 %, −0,62 à 0,06; très faible certitude des données probantes) et entre les voies intraveineuse vs orale (différence de moyennes, −0,60; IC 95 %, −1,20 à 0,01; faible certitude des données probantes). Pour la comparaison des voies orale vs rectale, nous avons trouvé des données probantes en faveur de la voie orale (différence de moyennes, −0,88; IC 95 %, −1,44 à −0,31; faible degré de certitude des données probantes). Peu d'études ont rapporté des résultats secondaires d'intérêt; en comparant les voies orale et rectale dans l'incidence des nausées et des vomissements, il n'y avait aucune preuve de différences (risque relatif, 1,20; IC 95 %, 0,81 à 1,78). CONCLUSION: Les données probantes disponibles sur l'effet de la voie d'administration de l'acétaminophène sur la douleur postopératoire chez les enfants sont très incertaines. Les résultats de contrôle de la douleur postopératoire et de vomissements postopératoires peuvent différer très peu entre la voie orale et la voie rectale. Des ERC mieux conçues et mieux exécutées sont nécessaires pour répondre à cette importante question clinique. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021286495); première soumission le 19 novembre 2021.

Intravenous lidocaine attenuates distention of the optical nerve sheath, a correlate of intracranial pressure, during endotracheal intubation.

BACKGROUND: By preventing hypoxia and hypercapnia, advanced airway management can save lives among patients with traumatic brain injury. During endotracheal intubation (ETI), tracheal stimulation causes an increase in intracranial pressure (ICP), which may impair brain perfusion. It has been suggested that intravenous lidocaine might attenuate this ICP response. We hypothesized that adding lidocaine to the standard induction medication for general anesthesia might reduce the ICP response to ETI. Here, we measured the optical nerve sheath diameter (ONSD) as a correlate of ICP and evaluated the effect of intravenous lidocaine on ONSD during and after ETI in patients undergoing anesthesia. METHODS: This double-blinded, randomized placebo-controlled trial included 60 patients with American Society of Anesthesiologists I or II physical status that were scheduled for elective surgery under general anesthesia. In addition to the standard anesthesia medication, 30 subjects received 1.5 mg/kg 1% lidocaine (0.15 mL/kg, ONSD lidocaine) and 30 received 0.15 mL/kg 0.9% NaCl (ONSD placebo). ONSDs were measured with ultrasound on the left eye, before (T0), during (T1), and 4 times after ETI (T2-5 at 5-min intervals). RESULTS: Compared to placebo, lidocaine did not significantly affect the baseline ONSD after anesthesia induction measured at T0. During ETI, the ONSD lidocaine was significantly smaller (ß=-0.24 mm P=0.022) than the ONSD placebo. At T4 and T5, the ONSD placebo increased steadily, up to 20 min after ETI, but the ONSD lidocaine tended to return to baseline levels. CONCLUSIONS: We found that the ONSD was distended during and after ETI in anesthetized patients, and intravenous lidocaine attenuated this effect.

Intraoperative Neuromonitoring in Patients with Intradural Extramedullary Spinal Cord Tumor: A Single-Center Case Series.

BACKGROUND: Intradural extramedullary spinal cord tumors (ID-EMSCT) make up 40% of all spinal neoplasms. Resection of these tumors is mostly conducted using intraoperative neuromonitoring (IONM). However, the literature shows heterogenous data on its added value for ID-EMSCT. The aim of this study is to define sensitivity and specificity of IONM in ID-EMSCT resection and to study possible correlations between preoperative, intraoperative, and postoperative variables and neurologic outcomes after ID-EMSCT resection. METHODS: Data of patients undergoing ID-EMSCT surgeries with IONM from January 2012 until July 2019 were examined. Using neurologic status 6 weeks and 1 year postoperatively, sensitivity and specificity for IONM were calculated. IONM test results and neurologic outcomes were paired to preoperative, intraoperative, and postoperative parameters. RESULTS: Data of 78 patients were analyzed. 6 weeks postoperatively, 14.10% of patients had worse neurologic status, decreasing to 9.84% 1 year postoperatively. Multimodal IONM showed a sensitivity of 0.73 (95% confidence interval [CI], 0.39-0.94) and a specificity of 0.78 (95% CI, 0.66-0.87) after 6 weeks, and a sensitivity of 1.00 (95% CI, 0.54-1.00) and a specificity of 0.71 (95% CI, 0.57-0.82) after 1 year. CONCLUSIONS: IONM yielded high to perfect sensitivity and high specificity. However, IONM signals did not always determine the extent of resection, and false-positive results did not always result in incomplete tumor resections, because of surgeons overruling IONM. Therefore, IONM cannot fully replace clinical judgment and other perioperative information.

Fluid loading therapy to prevent spinal hypotension in women undergoing elective caesarean section: Network meta-analysis, trial sequential analysis and meta-regression.

BACKGROUND: Fluid loading is one of the recognised measures to prevent hypotension due to spinal anaesthesia in women scheduled for a caesarean section. OBJECTIVE: We aimed to evaluate the current evidence on fluid loading in the prevention of spinal anaesthesia-induced hypotension. DESIGN: Systematic review and network meta-analysis with trial sequential analysis and meta-regression. DATA SOURCES: Medline, Epub, Embase.com (Embase and Medline), Cochrane Central, Web of Science and Google Scholar were used. ELIGIBILITY CRITERIA: Only randomised controlled trials were used. Patients included women undergoing elective caesarean section who received either crystalloid or colloid fluid therapy as a preload or coload. The comparator was a combination of either a different fluid or time of infusion. RESULTS: A total of 49 studies (4317 patients) were included. Network meta-analysis concluded that colloid coload and preload offered the highest chance of success (97 and 67%, respectively). Conventional meta-analysis showed that crystalloid preload is associated with a significantly higher incidence of maternal hypotension than colloid preload: risk ratio 1.48 (95% CI 1.29 to 1.69, P < 0.0001, I = 60%). However, this result was not supported by Trial Sequential Analysis. There was a significant dose-response effect for crystalloid volume preload (regression coefficient = -0.073), which was not present in the analysis of only double-blind studies. There was no dose-response effect for the other fluid regimes. CONCLUSION: Unlike previous meta-analysies, we found a lack of data obviating an evidence-based recommendation. In most studies, vasopressors were not given prophylactically as is recommended. Studies on the best fluid regimen in combination with prophylactic vasopressors are needed. Due to official european usage restrictions on the most studied colloid (HES), we recommend crystalloid coload as the most appropriate fluid regimen. TRIAL REGISTRATION: CRD42018099347.

Intrathecal hydrophilic opioids for abdominal surgery: a meta-analysis, meta-regression, and trial sequential analysis.

BACKGROUND: Intrathecal hydrophilic opioids decrease systemic opioid consumption after abdominal surgery and potentially facilitate enhanced recovery. A meta-analysis is needed to quantify associated risks and benefits. METHODS: A systematic search was performed to find RCTs investigating intrathecal hydrophilic opioids in abdominal surgery. Caesarean section and continuous regional or neuraxial techniques were excluded. Several subgroup analyses were prespecified. A conventional meta-analysis, meta-regression, trial sequential analysis, and provision of GRADE scores were planned. RESULTS: The search yielded 40 trials consisting of 2500 patients. A difference was detected in 'i.v. morphine consumption' at Day 1 {mean difference [MD] -18.4 mg, (95% confidence interval [CI]: -22.3 to -14.4)} and Day 2 (MD -25.5 mg [95% CI: -30.2 to -20.8]), pain scores at Day 1 in rest (MD -0.9 [95% CI: -1.1 to -0.7]) and during movement (MD -1.2 [95% CI: -1.6 to -0.8]), length of stay (MD -0.2 days [95% CI: -0.4 to -0.1]) and pruritus (relative risk 4.3 [95% CI: 2.5-7.5]) but not in nausea or sedation. A difference was detected for respiratory depression (odds ratio 5.5 [95% CI: 2.1-14.2]) but not when two small outlying studies were excluded (odds ratio 1.4 [95% CI: 0.4-5.2]). The level of evidence was graded as high for morphine consumption, in part because the required information size was reached. CONCLUSIONS: This study showed important opioid-sparing effects of intrathecal hydrophilic opioids. Our data suggest a dose-dependent relationship between the risk of respiratory depression and the dose of intrathecal opioids. Excluding two high-dose studies, intrathecal opioids have a comparable incidence of respiratory depression as the control group. CLINICAL TRIAL REGISTRATION: PROSPERO-registry: CRD42018090682.

The effect of midazolam as premedication on the quality of postoperative recovery after laparotomy: a randomized clinical trial.

PURPOSE: Despite the uncertain effects of anxiolytic premedication with benzodiazepines on the quality of postoperative recovery, perioperative benzodiazepine administration is still a common practice in many hospitals. We evaluated the effect of premedication with midazolam on the quality of recovery in hospitalized patients undergoing a laparotomy. METHODS: We conducted a single-centre randomized placebo-controlled, double-blinded clinical trial from July 2014 to September 2015. We included 192 patients aged > 18 yr scheduled for elective laparotomy with a planned postoperative stay of ≥ three days. Participants were randomized into two groups to receive either midazolam 3 mg or sodium chloride 0.9% intravenously as premedication prior to surgery. Patients were followed up for up to one week after surgery. The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day (POD) 3. The secondary outcomes included the QoR-40 score on POD 7, and the State-Trait Anxiety Inventory, State-Trait Anger Scale, Multidimensional Fatigue Inventory, and the Hospital Anxiety and Depression Scale scores. RESULTS: The mean (standard deviation) postoperative QoR-40 scores on POD 3 were not significantly different in the midazolam group compared with controls [166.4 (17.0) vs 163.9 (19.8), respectively; mean difference, 2.3; 95% confidence interval, - 2.9 to 8.4; P = 0.35]. There were no between-group differences in any of the secondary outcomes. CONCLUSIONS: Administration of midazolam as premedication for laparotomy patients did not improve the quality of recovery up to one week after surgery. General prescription of midazolam as premedication can be questioned and might only suit some patients. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01993459); registered 29 October, 2013.

Intraoperative Neuromonitoring in Patients with Intramedullary Spinal Cord Tumor: A Systematic Review, Meta-Analysis, and Case Series.

BACKGROUND: Intramedullary spinal cord tumors (IMSCT) comprise the least common types of spinal neoplasms; surgery is mostly conducted with intraoperative neuromonitoring (IONM). However, although IONM is widely used to prevent neurologic damage and many single-center studies have been reported, the added value, in terms of overall sensitivity and specificity, of different monitoring techniques used in IMSCT surgery remains to be clearly defined. OBJECTIVE: To summarize and review the reported evidence on the use of IONM in IMSCT surgery, including our own case series (n = 75 patients). METHODS: We systematically searched the literature published from January 2000 to February 2018. Articles included patients with IMSCT who underwent surgery with neuromonitoring. We estimated the sensitivity, specificity, 95% confidence interval (CI), positive likelihood ratio, and negative likelihood ratio. RESULTS: Of 1385 eligible articles, 31 were included in the systematic review. Fifteen of these articles were used for a meta-analysis, complemented with our own case series. All neuromonitoring modalities showed acceptable but not optimal test characteristics. For the indications used in the different studies, the motor evoked potentials approach showed the highest sensitivity (0.838; 95% CI, 0.703-0.919) and the best specificity (0.829; 95% CI, 0.668-0.921) for detecting neuronal injury. In our own case series, the extent of resection was significantly smaller in the false-positive group than in the true-negative group (P = 0.045). CONCLUSIONS: IONM showed high but not perfect sensitivity and specificity. IONM prevents neurologic damage but can also limit the extent of tumor resection. Prospective studies will have to define the definitive value of IONM.

A systematic review of the diagnostic accuracy of epidural wave form analysis to identify the epidural space in surgical and labor patients.

INTRODUCTION: Epidural failure due to misidentification of the epidural space is not uncommon. Epidural wave form analysis has been suggested to identify the epidural space. EVIDENCE ACQUISITION: A systematic literature search (Medline, Epub, Embase.com (Embase plus Medline), Cochrane Central, Web of Science, and Google Scholar) was performed to identify studies comparing epidural wave form analysis (index test) to epidural analgesia (reference test). EVIDENCE SYNTHESIS: Eight studies (3901 patients) were retrieved that provided data on diagnostic accuracy. These studies had a low risk of bias and of applicability concerns, as assessed by the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. One study did not observe an epidural wave form in parturients, a finding that was not corroborated in another study. Because the reference test was different across the studies we decided not aggregate the data. The sensitivity values of the individual studies varied between 0.81 and 1.00, for the specificity values between 0.42 and 1.00 were found. CONCLUSIONS: Our study suggests that epidural wave form analysis is a reliable method for identification of the epidural space that could become a useful adjunct especially in anticipated difficult catheter placements or in teaching situations. Further research is warranted to define the role of epidural wave form analysis in pregnant women.