Prospective real-time evaluation of the QTc interval variation after low-dose droperidol among emergency department patients.

OBJECTIVE: To assess the QTc interval variation after low-dose droperidol in a population of undifferentiated, stable, and non-agitated patients receiving droperidol in the emergency department. METHODS: Prospective cohort study of patients aged ≥12 years of age who received low-dose droperidol (≤ 2.5 mg) for indications other than acute behavioral disturbances. QTc intervals were monitored in real-time during pre-specified observation periods in the ED. Primary outcome was variation of QTc interval after droperidol administration, defined as the maximum delta (change) of QTc interval. Other outcomes included proportion of patients with a QTc ≥ 500 ms after droperidol, delta ≥ +60 ms, and incidence of clinical adverse events. Patients were monitored up to 30 min after IV bolus and up to 46 min after infusion. RESULTS: A total of 68 patients were included (mean age 42.1 years, 66.2% females). The median dose of droperidol was 1.875 mg (range 0.625 mg, 2.5 mg) and 94.1% received droperidol for headache management. Most patients received droperidol as a 2-min bolus (n = 41, 60.3%). The mean maximum delta of QTc interval after droperidol across all 68 patients was +29.9 ms (SD 15). A total of 12 patients (17.6%) experienced a QTc interval ≥ 500 ms during the observation period after droperidol, and 3 patients (4.4%) had a delta QTc ≥ +60 ms. There were no serious arrhythmias, such as TdP, or deaths among the 68 participants in this study (0/68). However, 13.2% (n = 9) had at least one non-serious adverse event including restlessness and/or anxiety. CONCLUSION: The QTc interval slightly increased after droperidol administration, but these prolongations were brief, mostly below 500 msec and did not lead to serious arrhythmias. The yield of continuous cardiac monitoring in patients receiving low doses of droperidol is likely low.

Midazolam Premedication Immediately Before Surgery Is Not Associated With Early Postoperative Delirium.

BACKGROUND: Postoperative delirium is common among older surgical patients and may be associated with anesthetic management during the perioperative period. The aim of this study is to assess whether intravenous midazolam, a short-acting benzodiazepine used frequently as premedication, increased the incidence of postoperative delirium. METHODS: Analyses of existing data were conducted using a database created from 3 prospective studies in patients aged 65 years or older who underwent elective major noncardiac surgery. Postoperative delirium occurring on the first postoperative day was measured using the confusion assessment method. We assessed the association between the use or nonuse of premedication with midazolam and postoperative delirium using a χ2 test, using propensity scores to match up with 3 midazolam patients for each control patient who did not receive midazolam. RESULTS: A total of 1266 patients were included in this study. Intravenous midazolam was administered as premedication in 909 patients (72%), and 357 patients did not receive midazolam. Those who did and did not receive midazolam significantly differed in age, Charlson comorbidity scores, preoperative cognitive status, preoperative use of benzodiazepines, type of surgery, and year of surgery. Propensity score matching for these variables and American Society of Anesthesiology physical status scores resulted in propensity score-matched samples with 1-3 patients who used midazolam (N = 749) for each patient who did not receive midazolam (N = 357). After propensity score matching, all standardized differences in preoperative patient characteristics ranged from -0.07 to 0.06, indicating good balance on baseline variables between the 2 exposure groups. No association was found between premedication with midazolam and incident delirium on the morning of the first postoperative day in the matched dataset, with odds ratio (95% confidence interval) of 0.91 (0.65-1.29), P = .67. CONCLUSIONS: Premedication using midazolam was not associated with higher incidence of delirium on the first postoperative day in older patients undergoing major noncardiac surgery.

The Facilitatory Effects of Adjuvant Pharmaceutics to Prolong the Duration of Local Anesthetic for Peripheral Nerve Block: A Systematic Review and Network Meta-analysis.

BACKGROUND: Peripheral nerve block (PNB) with perineural local anesthetic is used for anesthesia or analgesia with many benefits. To extend these benefits, various adjuvant drugs have been used to prolong the duration of analgesia. We aimed to evaluate the effectiveness of various adjuvants at prolonging the duration of sensory and motor blockade for PNB. METHODS: A network meta-analysis of placebo-controlled and active randomized controlled trials was performed comparing 10 adjuvants. Embase, PubMed, Web of Science, and Cochrane library were searched, with articles before May 21, 2020 included. Two authors independently selected studies and extracted data. The primary outcomes were sensory block (SB) and motor block (MB) time, and the secondary outcome was time of first analgesia rescue (FAR). Effect size measures were described as mean differences (MD) with 95% confidence intervals (CIs). Confidence in evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The study protocol was preregistered with the prospectively registered systematic reviews in health and social care international database (PROSPERO), as number CRD42020187866. RESULTS: Overall 16,364 citations were identified, of which 53 studies were included with data for 3649 patients. In network meta-analyses, 4 of 7 included treatment strategies were associated with more efficacious analgesia compared with placebo therapy, including dexamethasone (SB time: 5.73 hours, 95% CI, 4.16-7.30; MB time: 4.20 hours, 95% CI, 2.51-5.89; time of FAR: 8.71 hours, 95% CI, 6.63-10.79), dexmedetomidine (SB time: 4.51 hours, 95% CI, 3.52-5.50; MB time: 4.04 hours, 95% CI, 2.98-5.11; time of FAR: 5.25 hours, 95% CI, 4.08-6.43), fentanyl (SB time: 3.59 hours, 95% CI, 0.11-7.06; MB time: 4.42 hours, 95% CI, 0.78-8.06), and clonidine (SB time: 2.75 hours, 95% CI, 1.46-4.04; MB time: 2.93 hours, 95% CI, 1.69-4.16; time of FAR: 3.35 hours, 95% CI, 1.82-4.87). In a subgroup analysis, addition of dexamethasone to ropivacaine significantly increased the time of FAR when compared to dexmedetomidine (time of FAR: 5.23 hours, 95% CI, 2.92-7.54) or clonidine (time of FAR: 6.61 hours, 95% CI, 4.29-8.92) with ropivacaine. CONCLUSIONS: These findings provide evidence for the consideration of dexmedetomidine, dexamethasone, and clonidine as adjuvants to prolong the duration of PNB. The addition of dexamethasone to ropivacaine has a longer time of FAR compared with clonidine or dexmedetomidine.

The Effects of Anesthetics and Perioperative Medications on Immune Function: A Narrative Review.

Preclinical and clinical studies have sought to better understand the effect of anesthetic agents, both volatile and intravenous, and perioperative adjuvant medications on immune function. The immune system has evolved to incorporate both innate and adaptive components, which are delicately interwoven and essential for host defense from pathogens and malignancy. This review summarizes the complex and nuanced relationship that exists between each anesthetic agent or perioperative adjuvant medication studied and innate and adaptive immune function with resultant clinical implications. The most commonly used anesthetic agents were chosen for review including volatile agents (sevoflurane, isoflurane, desflurane, and halothane), intravenous agents (propofol, ketamine, etomidate, and dexmedetomidine), and perioperative adjuvant medications (benzodiazepines, opioids, nonsteroidal anti-inflammatory drugs [NSAIDs], and local anesthetic agents). Patients who undergo surgery experience varying combinations of the aforementioned anesthetic agents and adjuncts, depending on the type of surgery and their comorbidities. Each has unique effects on immunity, which may be more or less ideal depending on the clinical situation. Further study is needed to better understand the clinical effects of these relationships so that patient-specific strategies can be developed to improve surgical outcomes.

Risk Factors for Fentanyl-Induced Cough Following General Anesthesia in Adults: A Retrospective Study from a Single Center in China.

BACKGROUND Fentanyl-induced cough (FIC) during general anesthesia induction and postoperative nausea and vomiting are common complications, yet the risk factors for FIC remain controversial. This retrospective study was conducted at a single center in China and aimed to investigate the risk factors for fentanyl-induced cough following general anesthesia in adults. MATERIAL AND METHODS A total of 601 adult patients undergoing elective surgery were enrolled, and the incidence of FIC during general anesthesia induction and postoperative adverse events were recorded. The risk factors for FIC during general anesthesia induction and postoperative nausea and vomiting were assessed using multivariate logistic regression analysis. RESULTS The incidence of FIC, nausea, and vomiting were 21.8%, 6.3%, and 4.5%, respectively. The results of multivariate logistic regression analysis indicated that pharyngitis history was associated with an increased risk of FIC during general anesthesia induction (odds ratio [OR]: 2.852; 95% confidence interval [CI]: 1.698-4.792; P<0.001), whereas use of lidocaine could protect against FIC risk (OR: 0.649; 95% CI: 0.557-0.757; P<0.001). However, the characteristics of patients were not associated with the risk of postoperative nausea and vomiting. CONCLUSIONS The findings from this study showed that a history of pharyngitis increased the risk of FIC, while the use of lidocaine was associated with a reduced risk of FIC. The risk of postoperative nausea and vomiting was not affected by fentanyl use or patient characteristics.

Effect of intravenous dexamethasone on the anaesthetic characteristics of peripheral nerve block: a double-blind, randomised controlled, dose-response volunteer study.

BACKGROUND: Intravenous dexamethasone is thought to prolong the duration of peripheral nerve block, but the dose-response relationship remains unclear. The aim of this volunteer study was to evaluate the dose-response effect of i.v. dexamethasone on the prolongation of median nerve block. METHODS: In a double-blind, randomised controlled study, 18 volunteer subjects received two median nerve blocks separated by a washout period. One block was conducted alongside an infusion of saline and the other alongside i.v. dexamethasone 2, 4, or 8 mg. The primary outcome was time to return of normal pinprick sensation. Secondary outcomes included thermal quantitative sensory testing (QST) for the time to return of cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), area under QST curves, grip strength, and the incidence of adverse effects. RESULTS: The primary outcome, time to recovery of pinprick sensation, was similar between volunteers receiving saline or i.v. dexamethasone, regardless of dose (P=0.99). The time to recovery of QST milestones was similar between groups, although area under QST curves indicated prolongation of CDT (0 vs 8 mg, P=0.002) and WDT (0 vs 2 mg, P=0.008; 0 vs 4 mg, P=0.001; 0 vs 8 mg, P<0.001). There was no difference in motor recovery or adverse effects. CONCLUSIONS: Intravenous dexamethasone failed to significantly prolong the duration of pinprick anaesthesia regardless of dose. However, area under QST curve analysis indicated a dose-independent prolongation of CDT and WDT, the clinical significance of which is unclear. CLINICAL TRIAL REGISTRATION: NCT02864602 (clinicaltrials.gov).

Sedation During Endoscopy in Patients with Cirrhosis: Safety and Predictors of Adverse Events.

BACKGROUND: Sedation during endoscopy in cirrhotic patients is typically via moderate sedation, most commonly using a combination of a benzodiazepine (i.e., midazolam) and narcotic (i.e., fentanyl) or with propofol using monitored anesthesia care (MAC). Here, we examined the safety of moderate sedation and MAC in patients with cirrhosis. METHODS: This retrospective cohort study of cirrhotic patients undergoing endoscopy from a large academic medical center between 2010 and 2014 examined extensive clinical data including the following: past history, physical findings, laboratory results, and procedural adverse events. Adverse events were defined a priori and included hypoxia, hypotension, bleeding, and death. RESULTS: We identified 2618 patients with cirrhosis who underwent endoscopic procedures; the mean age was 56 years, 36% were female, the mean Child-Pugh score was 9.3 (IQR: 8, 11), and Charlson Comorbidity Index score was 3.2 (IQR: 1, 4); 1157 had MAC; and 1461 had moderate sedation. There was no difference in the frequency of adverse events in MAC and moderate sedation groups, with a total of 15 adverse events (7/1157 MAC and 8/1461 moderate sedation). The most common procedure performed was esophagogastroduodenoscopy (EGD, n = 1667) and was associated with 10 adverse events. Overall, adverse events included bradycardia (1), hypoxia (7), bleeding (5), laryngospasm (1), and perforation (1). The frequency was similar for EGD, ERCP, and colonoscopy-each at a rate of 0.6%. CONCLUSIONS: Adverse events in cirrhotic patients undergoing endoscopy appeared to be similar with moderate sedation or MAC, and the frequency was the same for different types of procedures.

Droperidol Reduces Postoperative Nausea and Vomiting and Supports the Continuation of Intravenous Patient-Controlled Analgesia with Fentanyl.

PURPOSE: To examine the impact of adding droperidol to fentanyl-based intravenous patient- controlled analgesia (IVPCA) on the discontinuation of IVPCA use due to postoperative nausea and vomiting (PONV). METHODS: Patients who underwent surgeries other than abdominal surgeries and used IVPCA between April 2014 and March 2018 were selected. Patients using IVPCA with fentanyl alone were compared to patients using droperidol added to IVPCA. Patients were allocated to one of two groups depending on the drug used for IVPCA: 1) control group, fentanyl alone; 2) droperidol group, droperidol with fentanyl. The primary endpoint was the discontinuation of IVPCA due to PONV. Secondary endpoints included PONV within 48 hours after surgery, the number of antiemetics used, pain score, and adverse effects. Propensity score matching was used to control the differences in clinical features among patients. RESULTS: Among the 793 patients initially enrolled in this study, 145 were excluded via propensity score matching; 364 of the remaining patients received IVPCA supplemented with droperidol. Propensity score matching showed that discontinuation of IVPCA due to PONV was significantly decreased in the droperidol group compared to the control group (P = 0.01). Further, compared with the control group, the droperidol group had reduced nausea up to 24 hours after surgery (P < 0.01), and the number of vomiting episodes and use of antiemetics decreased within 12 hours after surgery (P < 0.01). CONCLUSIONS: The addition of droperidol to IVPCA is associated with a decrease in PONV, as well as the improved continuation of pain treatment with fentanyl-based IVPCA, similar to IVPCA with morphine. However, it is necessary to monitor the side effects of this treatment.

Local Anesthesia Thoracoscopy with versus without Midazolam: A Randomized Controlled Trial.

BACKGROUND: Medical thoracoscopy is the gold standard for the diagnosis of pleural diseases. To date, no consensus exists regarding the choice of sedative and analgesic agents in patients undergoing local anesthetic thoracoscopy (LAT), and questions are raised as to whether sedatives may add to respiratory side effects. OBJECTIVE: The aim of the study was to test the hypothesis that administration of midazolam associated with lidocaine versus lidocaine alone in patients with LAT adds to respiratory side effects. METHODS: We randomly assigned 80 patients to a 1:1 study to 2 groups: local anesthesia by lidocaine (n = 40) versus lidocaine and midazolam (n = 40), with the primary end point being the mean lowest oxygen saturation. The secondary end points were cardiovascular parameters, complications, days of drainage, hospital stay, and patients' quality of life (QoL) as assessed by a visual analog scale (VAS). RESULTS: The mean age of all patients was 66.6 ± 13.1 years. The study comprised 50 males (62.5%). No difference was observed in the demographics between the 2 groups. No significant difference was observed between the 2 groups in oxygen saturation (primary end point). A significant difference was observed in favor of the midazolam group regarding the QoL assessed by VAS. CONCLUSION: Midazolam does not add to respiratory side effects when it is used with lidocaine for LAT, while patients' QoL is actually improved in this group. Therefore, in our department, we changed our startegy in favor of the association of lidocaine and midazolam.

Effect of Midazolam on Vestibular Signs in Two Geriatric Dogs with Vestibular Disease.

An abrupt balance impairment, including leaning, falling, and rolling, occurred after IV administration of 0.2 mg/kg midazolam as a preanesthetic medication in two geriatric dogs with a history of nystagmus and head tilt. In the second case, leaning, falling, and rolling recurred after recovery from general anesthesia but gradually ceased after IV administration of 0.01 mg/kg flumazenil. These two cases suggest that the IV administration of midazolam was responsible for the balance impairment in dogs who were suspected to have idiopathic peripheral vestibular disease.

Evaluation of a Safety Protocol for the Management of Thirst in the Postoperative Period.

PURPOSE: To associate medications, anesthetic techniques, and clinical conditions that interfere in the time of patient approval in the safety protocol for thirst management. DESIGN: A quantitative, analytical, and longitudinal study conducted in Southern Brazil. METHODS: A nonprobabilistic sample, of 203 adult patients in the immediate postoperative period, evaluated every 15 minutes for 1 hour. FINDINGS: A general prevalence of thirst of 67.7%, and mean intensity of 6.38. Fentanyl, morphine, rocuronium, and sevoflurane increased lack of approval in the protocol within 30 minutes (P < .05). General anesthesia (P < .0001) and level of consciousness (95.4%) presented the highest nonapproval rates. CONCLUSIONS: Anesthetics and general anesthesia delayed protocol approval; however, after 30 minutes, 75.4% of patients had been approved. Level of consciousness was the main criterion of disapproval. The protocol identified crucial clinical conditions that made it impossible for the patient to receive thirst relief strategies and demonstrated that thirst can be satiated precociously with safety.

The Effect of Dexmedetomidine on Propofol Requirements During Anesthesia Administered by Bispectral Index-Guided Closed-Loop Anesthesia Delivery System: A Randomized Controlled Study.

BACKGROUND: Dexmedetomidine, a selective α2-adrenergic agonist currently approved for continuous intensive care unit sedation, is being widely evaluated for its role as a potential anesthetic. The closed-loop anesthesia delivery system (CLADS) is a method to automatically administer propofol total intravenous anesthesia using bi-spectral index (BIS) feedback and attain general anesthesia (GA) steady state with greater consistency. This study assessed whether dexmedetomidine is effective in further lowering the propofol requirements for total intravenous anesthesia facilitated by CLADS. METHODS: After ethics committee approval and written informed consent, 80 patients undergoing elective major laparoscopic/robotic surgery were randomly allocated to receive GA with propofol CLADS with or without the addition of dexmedetomidine. Quantitative reduction of propofol and quality of depth-of-anesthesia (primary objectives), intraoperative hemodynamics, incidence of postoperative adverse events (sedation, analgesia, nausea, and vomiting), and intraoperative awareness recall (secondary objectives) were analyzed. RESULTS: There was a statistically significant lowering of propofol requirement (by 15%) in the dexmedetomidine group for induction of anesthesia (dexmedetomidine group: mean ± standard deviation 0.91 ± 0.26 mg/kg; nondexmedetomidine group: 1.07 ± 0.23 mg/kg, mean difference: 0.163, 95% CI, 0.04-0.28; P = .01) and maintenance of GA (dexmedetomidine group: 3.25 ± 0.97 mg/kg/h; nondexmedetomidine group: 4.57 ± 1.21 mg/kg/h, mean difference: 1.32, 95% CI, 0.78-1.85; P < .001). The median performance error of BIS control, a measure of bias, was significantly lower in dexmedetomidine group (1% [-5.8%, 8%]) versus nondexmedetomidine group (8% [2%, 12%]; P = .002). No difference was found for anesthesia depth consistency parameters, including percentage of time BIS within ±10 of target (dexmedetomidine group: 79.5 [72.5, 85.3]; nondexmedetomidine group: 81 [68, 88]; P = .534), median absolute performance error (dexmedetomidine group: 12% [10%, 14%]; nondexmedetomidine group: 12% [10%, 14%]; P = .777), wobble (dexmedetomidine group: 10% [8%, 10%]; nondexmedetomidine group: 8% [6%, 10%]; P = .080), and global score (dexmedetomidine group: 25.2 [23.1, 35.8]; nondexmedetomidine group: 24.7 [20, 38.1]; P = .387). Similarly, there was no difference between the groups for percentage of time intraoperative heart rate and mean arterial pressure remained within 20% of baseline. However, addition of dexmedetomidine to CLADS propofol increased the incidence of significant bradycardia (dexmedetomidine group: 14 [41.1%]; nondexmedetomidine group: 3 [9.1%]; P = .004), hypotension (dexmedetomidine group: 9 [26.5%]; nondexmedetomidine group: 2 [6.1%]; P = .045), and early postoperative sedation. CONCLUSIONS: The addition of dexmedetomidine to propofol administered by CLADS was associated with a consistent depth of anesthesia along with a significant decrease in propofol requirements, albeit with an incidence of hemodynamic depression and early postoperative sedation.

Efficacy and Safety of Fentanyl in Combination with Midazolam in Children on Mechanical Ventilation.

BACKGROUND: To evaluate the efficacy and safety of fentanyl for sedation therapy in mechanically ventilated children. METHODS: This was a double-blind, randomized controlled trial of mechanically ventilated patients between 2 months and 18 years of age. Patients were randomly divided into two groups; the control group with midazolam alone, and the combination group with both fentanyl and midazolam. The sedation level was evaluated using the Comfort Behavior Scale (CBS), and the infusion rates were adjusted according to the difference between the measured and the target CBS score. RESULTS: Forty-four patients were recruited and randomly allocated, with 22 patients in both groups. The time ratio of cumulative hours with a difference in CBS score (measured CBS-target CBS) of ≥ 4 points (i.e., under-sedation) was lower in the combination group (median, 0.06; interquartile range [IQR], 0-0.2) than in the control group (median, 0.15; IQR, 0.04-0.29) (P < 0.001). The time ratio of cumulative hours with a difference in CBS score of ≥ 8 points (serious under-sedation) was also lower in the combination group (P < 0.001). The cumulative amount of midazolam used in the control group (0.11 mg/kg/hr; 0.07-0.14 mg/kg/hr) was greater than in the combination group (0.07 mg/kg/hr; 0.06-0.11 mg/kg/hr) (P < 0.001). Two cases of hypotension in each group were detected but coma and ileus, the major known adverse reactions to fentanyl, did not occur. CONCLUSION: Fentanyl combined with midazolam is safe and more effective than midazolam alone for sedation therapy in mechanically ventilated children. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02172014.

Use of Fentanyl During Percutaneous Coronary Interventions: Safety and Drawbacks.

Over the last years, fentanyl, a potent synthetic µ receptor-stimulating opioid, has become one of the most used drugs for both procedural analgesia and sedation in patients undergoing coronary angiography (CA) and/or percutaneous coronary intervention (PCI). However, few studies have been performed to evaluate the efficacy and the impact of this drug in patients with coronary artery disease (CAD) treated with PCI. Most of the previous studies have investigated the self-reported discomfort pain, demonstrating that patients premedicated with fentanyl generally reported a lower pain/discomfort when compared to placebo, benzodiazepines, or local anesthesia at the site of the artery cannulation, without significant variation in the hemodynamic response. The biochemical properties of fentanyl have been used to prevent the radial arterial spasm, which represents one of the major causes of the access site cross-over during PCI, experienced when radial artery cannulation has failed and successful access can be obtained only switching to an alternative arterial route, as the ulnar or the femoral artery. However, some unresolved problems, as fentanyl-induced hypothermia and delayed absorption of P2Y12 inhibitors required further investigations.

Multimodal General Anesthesia: Theory and Practice.

Balanced general anesthesia, the most common management strategy used in anesthesia care, entails the administration of different drugs together to create the anesthetic state. Anesthesiologists developed this approach to avoid sole reliance on ether for general anesthesia maintenance. Balanced general anesthesia uses less of each drug than if the drug were administered alone, thereby increasing the likelihood of its desired effects and reducing the likelihood of its side effects. To manage nociception intraoperatively and pain postoperatively, the current practice of balanced general anesthesia relies almost exclusively on opioids. While opioids are the most effective antinociceptive agents, they have undesirable side effects. Moreover, overreliance on opioids has contributed to the opioid epidemic in the United States. Spurred by concern of opioid overuse, balanced general anesthesia strategies are now using more agents to create the anesthetic state. Under these approaches, called "multimodal general anesthesia," the additional drugs may include agents with specific central nervous system targets such as dexmedetomidine and ones with less specific targets, such as magnesium. It is postulated that use of more agents at smaller doses further maximizes desired effects while minimizing side effects. Although this approach appears to maximize the benefit-to-side effect ratio, no rational strategy has been provided for choosing the drug combinations. Nociception induced by surgery is the primary reason for placing a patient in a state of general anesthesia. Hence, any rational strategy should focus on nociception control intraoperatively and pain control postoperatively. In this Special Article, we review the anatomy and physiology of the nociceptive and arousal circuits, and the mechanisms through which commonly used anesthetics and anesthetic adjuncts act in these systems. We propose a rational strategy for multimodal general anesthesia predicated on choosing a combination of agents that act at different targets in the nociceptive system to control nociception intraoperatively and pain postoperatively. Because these agents also decrease arousal, the doses of hypnotics and/or inhaled ethers needed to control unconsciousness are reduced. Effective use of this strategy requires simultaneous monitoring of antinociception and level of unconsciousness. We illustrate the application of this strategy by summarizing anesthetic management for 4 representative surgeries.

Caudal and intravenous dexamethasone as an adjuvant to pediatric caudal block: A systematic review and meta-analysis.

BACKGROUND: Dexamethasone has become a popular additive for regional anesthesia. The aim of this meta-analysis was to assess the effectiveness of this additive on the duration of postoperative analgesia, postoperative vomiting, and possible adverse events in pediatrics. METHODS: We searched databases, conference records, and registered trials for randomized controlled trials. The databases included the Cochrane Library, JBI Database of Systematic Reviews, PubMed, ISI Web of Knowledge, Science-Direct, and Embase. Odds ratio, weighted mean difference, and the corresponding 95% confidence intervals were calculated using the REVMAN software, version 5.3, for data synthesis and statistical analysis, which following the PRISMA statement. The main outcomes were duration of postoperative analgesia (time from the end of surgery to first administration of analgesics as evidenced by a pain score) and postoperative vomiting. RESULTS: Seven studies were selected for this meta-analysis, involving 647 pediatric patients. All the patients were randomized to receive caudal or intravenous dexamethasone with caudal block (experimental group) or plain caudal block (control group). There was significantly longer duration of postoperative analgesia in the experimental group compared with control group (weighted mean difference: 238.40 minutes; 95% CI: 193.41-283.40; P < .00001). The experimental group had fewer patients who needed analgesics after surgery (odds ratio: 0.18 minutes; 95% CI: 0.05-0.66; P = .009). Additionally, the number of subjects who remained pain-free to 2, 6, 24, and 48 hours after operation was significantly greater in the experimental group than control group. Side effects in these 2 groups were comparable (odds ratio: 0.94; 95% CI: 0.34-2.56; P = .90). The incidence of postoperative vomiting was significantly decreased in the experimental group compared with control group (odds ratio: 0.29; 95% CI: 0.13-0.63; P = .002). CONCLUSION: Caudal and intravenous dexamethasone could provide longer duration of postoperative analgesia and reduced the incidence of postoperative vomiting with comparable adverse effects than plain caudal block. However, any additive to the caudal space carries with it the potential for neurotoxicity and that caution should always be exercised when weighting the risks and benefits of any additive. The result was influenced by small numbers of participants and significant heterogeneity.

Effect of Atropine With Propofol vs Atropine With Atracurium and Sufentanil on Oxygen Desaturation in Neonates Requiring Nonemergency Intubation: A Randomized Clinical Trial.

Importance: Propofol or a combination of a synthetic opioid and muscle relaxant are both recommended for premedication before neonatal intubation but have yet to be compared. Objective: To compare prolonged desaturation during neonatal nasotracheal intubation after premedication with atropine-propofol vs atropine-atracurium-sufentanil treatment. Design, Setting, and Participants: Multicenter, double-blind, randomized clinical trial (2012-2016) in 6 NICUs in France that included 173 neonates requiring nonemergency intubation. The study was interrupted due to expired study kits and lack of funding. Interventions: Eighty-nine participants were randomly assigned to the atropine-propofol group and 82 to the atropine-atracurium-sufentanil group before nasotracheal intubation. Main Outcomes and Measures: The primary outcome was prolonged desaturation (Spo2 <80% lasting > 60 seconds), using intention-to-treat analysis using mixed models. Secondary outcomes assessed the characteristics of the procedure and its tolerance. Results: Of 173 neonates randomized (mean gestational age, 30.6 weeks; mean birth weight, 1502 g; 71 girls), 171 (99%) completed the trial. Of 89 infants, 53 (59.6%) in the atropine-propofol group vs 54 of 82 (65.9%) in the atropine-atracurium-sufentanil group achieved the primary outcome (adjusted RD, -6.4; 95% CI, -21.0 to 8.1; P = .38). The atropine-propofol group had a longer mean procedure duration than did the atropine-atracurium-sufentanil group (adjusted RD, 1.7 minutes; 95% CI, 0.1-3.3 minutes; P = .04); a less frequent excellent quality of sedation rate, 51.7% (45 of 87) vs 92.6% (75 of 81; P < .001); a shorter median time to respiratory recovery, 14 minutes (IQR, 8-34 minutes) vs 33 minutes (IQR, 15-56 minutes; P = .002), and shorter median time to limb movement recovery, 18 minutes (IQR, 10-43 minutes) vs 36 minutes (IQR, 19-65 minutes; P = .003). In the 60 minutes after inclusion, Spo2 was preserved significantly better in the atropine-propofol group (time × treatment interaction P = .02). Of the atropine-propofol group 20.6% had head ultrasound scans that showed worsening intracranial hemorrhaging (any or increased intraventricular hemorrhage) in the 7 days after randomization vs 17.6% in the atropine-atracurium-sufentanil group (adjusted RD, 1.2; 95% CI, -13.1 to 15.5, P = .87). Severe adverse events occurred in 11% of the atropine-propofol group and in 20% of the atropine-atracurium-sufentanil group. Conclusions and Relevance: Among neonates undergoing nonemergency nasotracheal intubation, the frequency of prolonged desaturation did not differ significantly between atropine used with propofol or atropine used with atracurium and sufentanil. However, the study may have been underpowered to detect a clinically important difference, and further research may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01490580, EudraCT number: 2009-014885-25.

Bolus Administration of Fentanyl and Midazolam for Colonoscopy Increases Endoscopy Unit Efficiency and Safety Compared With Titrated Sedation.

BACKGROUND & AIMS: Guidelines recommend slow titration of sedatives for moderate sedation. Bolus sedation, in which a larger weight-based dose of medication is given upfront, has been shown in a single trial to be beneficial. We evaluated the effects of bolus sedation on procedural safety, efficiency, and patient experience. METHODS: We performed a retrospective analysis of colonoscopies performed between April 2010 and April 2011 at Duke Medical Center. Colonoscopies before October 2010 were performed with nurse-directed titration of sedative (n = 966); colonoscopies performed after October 2010 were performed with physician-directed administration of bolus sedative (n = 699). We compared sedation and recovery times, medication doses, and adverse events between groups. We also compared patient satisfaction in a subset of patients from each group. Data were compared using the chi-square test for categorical variables and Wilcoxon rank sum test for continuous and ordinal categorical variables. RESULTS: Patients in the bolus group had a shorter sedation time (6.0 min) than patients in the titration group (13.0 min; P < .01) and a slightly longer colonoscopy time (25.0 min vs 24.0 min in the titration group; P < .01). Recovery time did not differ significantly between groups (53.0 min in the bolus group vs 52.1 min in the titration group; P = .07). Patients in the bolus group received lower weight-adjusted doses of fentanyl (1.71 µg/kg vs 1.89 µg/kg in the titration group) and midazolam (0.065 mg/kg vs 0.075 mg/kg in the titration group). A smaller proportion of patients in the bolus sedative group developed hypotension (12.7% vs 17.9% in the titration group; P < .01). These findings persisted even after adjustment for baseline patient age, race, sex, smoking status, alcohol use, body mass index, and American Society of Anesthesiologists' classification. CONCLUSIONS: In a retrospective study of patients undergoing colonoscopy, we found that compared with titrated administration of sedative, bolus dosing improves endoscopy unit efficiency and safety and decreases the amount of sedative required. This benefit does not come at the expense of the patient experience.

Hypoxemia after single-shot anesthesia in common marmosets.

BACKGROUND: It remains unknown how single-shot anesthesia influences physical parameters, especially respiratory function and blood oxygen level of common marmosets (Callithrix jacchus) which came to be used for laboratory research. METHODS: We measured blood oxygen levels, both before and after oxygenation, in 13 common marmosets under two single-shot anesthesia conditions: ketamine/xylazine/atropine and alphaxalone. RESULTS AND CONCLUSIONS: We found that SpO2 values decreased to about 80% in the ketamine/xylazine/atropine protocol and fell just below 90% in the alphaxalone protocol. We observed a clear decrease in PaO2 values under the anesthetized condition compared to the awake condition. Our data indicate that single-shot anesthesia may cause hypoxemia in marmosets. Previous studies on other non-human primate have reported no SpO2 decrease and hypoxemia; thus, our experiment suggests that marmosets may have a more fragile respiratory system and require intensive veterinary care during anesthesia.

Methylprednisolone plus diazepam i.v. as bridge therapy for medication overuse headache.

Management of medication overuse headache (MOH) requires abrupt suspension of overused drugs either alone or in association with a detoxification protocol to prevent withdrawal. However, there is no consensus about which suspension strategy is the most effective. Moreover, reliable data about the possible mid-term effect of detoxification are not available. The objective of this study was to evaluate whether a bridge therapy consisting of a 5-day i.v. infusion of methylprednisolone and diazepam determines a significant reduction in headache frequency and drug assumption during the detoxification protocol (day 5) and in the first 3 months in patients with MOH. We conducted a retrospective non-randomized before-and-after study comparing patients with MOH undergoing a bridge therapy protocol (5-day infusion of methylprednisolone, diazepam) with those who refused the treatment and were only recommended to suspend overused painkillers. Both groups started a prophylactic treatment and were followed-up for 3 months. At day 5, 82% of our patients were headache-free; moreover, 48% of the patients did not take any painkiller during the 5-day treatment. Three months after, the intervention group showed a greater reduction of monthly headache days (9.4 vs 3.0) and drugs (19.7 vs 6.5), a greater rate of patients with a ≥ 50% reduction of monthly headaches (p = 0.019) and symptomatic drug consumption (p = 0.000), than the control group. The methylprednisolone and diazepam detoxification protocol reduced headache attacks and drug assumption immediately and in the first 3 months after the intervention, concurring to improve the effect of a new prophylactic therapy.