Safety and Efficacy of the Combination of Propofol and Ketamine for Procedural Sedation/Anesthesia in the Pediatric Population: A Systematic Review and Meta-analysis.

BACKGROUND: Drugs such as propofol and ketamine are used alone or in combination to provide sedation for medical procedures in children. The purpose of this systematic review was to compare the safety and effectiveness of propofol and ketamine to other drug regimens. METHODS: We searched Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Web of Science, and the grey literature (meta-Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar) for randomized controlled studies comparing intravenous propofol and ketamine to any other single or combination drug regimen administered to children undergoing diagnostic or therapeutic procedures. Meta-analyses were performed for primary (hemodynamic and respiratory adverse events) and secondary outcomes using RevMan 5.3. We assessed the risk of bias and the certainty (quality) evidence for all outcomes using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Twenty-nine studies were included for analysis. Based on low-to-moderate quality evidence, we concluded that the use of propofol and ketamine may result in a slight-to-small reduction in the risk of hypotension, bradycardia, and apnea, and a slight increase in the risk of tachycardia, hypertension, and other respiratory adverse events, such as cough or laryngospasm. The ratio of propofol to ketamine and comparator drug regimen subgroups effects were important for desaturation and some secondary outcomes. CONCLUSIONS: The use of propofol and ketamine had a minimal effect on the incidence of adverse events and other secondary outcomes. Large-scale studies are required to more accurately estimate adverse event rates and the effects of propofol and ketamine on patient-important outcomes.

Cardiovascular effects of intravenous vatinoxan (MK-467) in medetomidine-tiletamine-zolazepam anaesthetised red deer (Cervus elaphus).

OBJECTIVE: To determine the effect of intravenous vatinoxan administration on bradycardia, hypertension and level of anaesthesia induced by medetomidine-tiletamine-zolazepam in red deer (Cervus elaphus). STUDY DESIGN AND ANIMALS: A total of 10 healthy red deer were included in a randomised, controlled, experimental, crossover study. METHODS: Deer were administered a combination of 0.1 mg kg-1 medetomidine hydrochloride and 2.5 mg kg-1 tiletamine-zolazepam intramuscularly, followed by 0.1 mg kg-1 vatinoxan hydrochloride or equivalent volume of saline intravenously (IV) 35 minutes after anaesthetic induction. Heart rate (HR), mean arterial blood pressure (MAP), respiration rate (fR), end-tidal CO2 (Pe'CO2), arterial oxygen saturation (SpO2), rectal temperature (RT) and level of anaesthesia were assessed before saline/vatinoxan administration (baseline) and at intervals for 25 minutes thereafter. Differences within treatments (change from baseline) and between treatments were analysed with linear mixed effect models (p < 0.05). RESULTS: Maximal (81 ± 10 beats minute-1) HR occurred 90 seconds after vatinoxan injection and remained significantly above baseline (42 ± 4 beats minute-1) for 15 minutes. MAP significantly decreased from baseline (122 ± 10 mmHg) to a minimum MAP of 83 ± 6 mmHg 60 seconds after vatinoxan and remained below baseline until end of anaesthesia. HR remained unchanged from baseline (43 ± 5 beats minute-1) with the saline treatment, whereas MAP decreased significantly (112 ± 16 mmHg) from baseline after 20 minutes. Pe'CO2, fR and SpO2 showed no significant differences between treatments, whereas RT decreased significantly 25 minutes after vatinoxan. Level of anaesthesia was not significantly influenced by vatinoxan. CONCLUSIONS AND CLINICAL RELEVANCE: Vatinoxan reversed hypertension and bradycardia induced by medetomidine without causing hypotension or affecting the level of anaesthesia in red deer. However, the effect on HR subsided 15 minutes after vatinoxan IV administration. Vatinoxan has the potential to reduce anaesthetic side effects in non-domestic ruminants immobilised with medetomidine-tiletamine-zolazepam.

[Intoxication with prilocaine/lidocaine can cause serious methemoglobinemia]. / Överdos av prilokain/lidokain kan ge svår methemoglobinemi - Tre fall där krämen gett toxiska effekter hos spädbarn.

Prilocaine/lidocaine is widely used as local anesthetic in children for cannulation and minor surgical procedures. Usually it is unproblematic but it is important to adhere to recommended dose to avoid serious complications. Excessive amount of prilocaine/lidocaine, large application area, prolonged application time or repeated application can, especially in infants, cause methemoglobinemia with clinical symptoms. In severe cases intensive care and antidote treatment with Methylene blue may be required. We report three infants who were overdosed with prilocaine/lidocaine, two of them due to incorrect use after circumcision and one premature baby where prilocaine/lidocaine was not removed in time. Two of the babies had MetHb levels > 33% and were seriously affected with hypoxia, tachycardia and fatigue. After Methylene blue was given the infants recovered within 15 minutes and MetHb levels returned to normal.

Stellate ganglion block and cardiac sympathetic denervation in patients with inappropriate sinus tachycardia.

BACKGROUND: Inappropriate sinus tachycardia (IST) remains a clinical challenge because patients often are highly symptomatic and not responsive to medical therapy. OBJECTIVE: To study the safety and efficacy of stellate ganglion (SG) block and cardiac sympathetic denervation (CSD) in patients with IST. METHODS: Twelve consecutive patients who had drug-refractory IST (10 women) were studied. According to a prospectively initiated protocol, five patients underwent an electrophysiologic study before and after SG block (electrophysiology study group). The subsequent seven patients had ambulatory Holter monitoring before and after SG block (ambulatory group). All patients underwent SG block on the right side first, and then on the left side. Selected patients who had heart rate reduction ≥15 beats per minute (bpm) were recommended to consider CSD. RESULTS: The mean (SD) baseline heart rate (HR) was 106 (21) bpm. The HR significantly decreased to 93 (20) bpm (P = .02) at 10 minutes after right SG block and remained significantly slower at 97(19) bpm at 60 minutes. Left SG block reduced HR from 99 (21) to 87(16) bpm (P = .02) at 60 minutes. SG block had no significant effect on blood pressure or HR response to isoproterenol or exercise (all P > .05). Five patients underwent right (n = 4) or bilateral (n = 1) CSD. The clinical outcomes were heterogeneous: one patient had complete and two had partial symptomatic relief, and two did not have improvement. CONCLUSION: SG blockade modestly reduces resting HR but has no significant effect on HR during exercise. Permanent CSD may have a modest role in alleviating symptoms in selected patients with IST.

Comparison of propofol-ketamine versuspropofol-remifentanil in children anaesthetized for gastroscopy.

BACKGROUND: The search for ideal anaesthesia is still an open research issue. The aim of the study was to evaluate and compare two methods of general anaesthesia with preserved own breath - propofol with ketamine and propofol with remifentanil - in children anaesthetized for gastroscopy. METHODS: The study included 90 children enrolled for elective endoscopy of the upper gastrointestinal tract under general anaesthesia. The patients were randomized to one of two groups: Group K consisted of children anesthetized with propofol and ketamine, Group R included children anesthetized with propofol and remifentanil. Parameters monitored during anaesthesia were induction time, respiratory and circulatory parameters, adverse events, waking time and the child's condition after regaining consciousness. RESULTS: The groups differed significantly in time of induction of anaesthesia (Group K 3 ± 1 min vs. Group R 4 ± 2.5 min; P < 0.001), waking time (Group R 4 ± 4.5 min vs. Group K 6 ± 5 min; P < 0.01), condition of the child after regaining consciousness (Group R 90.9% calm, Group of K 54% confused; P < 0.001) and evaluation of test conditions in the opinion of the gastroenterologist (in favour of Group K; P < 0.05). CONCLUSIONS: Both methods of anaesthesia presented in the paper are safe and can be used in children to perform endoscopy. Combining propofol with ketamine allows fast induction of anaesthesia and creates very good conditions for the examination. Combining propofol with remifentanil allows fast and full return of consciousness after anaesthesia.

Incidence and impact factors of intraoperative loss of light perception under sub-Tenon's anesthesia in patients with macular diseases.

PURPOSE: To investigate the incidence and impact factors of intraoperative loss of light perception (LP) under sub-Tenon's anesthesia in patients with macular diseases. METHODS: Eighty-five consecutive patients received standard phacoemulsification combined pars plana vitrectomy (PPV) under sub-Tenon's anesthesia. At several checkpoints during the surgery (the end of phacoemulsification, the end of vitrectomy, and the end of surgery), participants were interviewed about whether they had LP or not after removing the influence of contralateral eye and the photo-bleaching effect. In patients treated with retinal photocoagulation, visual experience on laser flashes was evaluated. RESULTS: Under routine draping, no patients reported loss of LP at all the checkpoints. When the contralateral eye was tightly covered, the rates of LP loss were 84.7%, 97.6%, and 87.1% at the end of phacoemulsification, the end of vitrectomy, and the end of surgery, respectively. When the photo-bleaching effect was also removed, the rates of LP loss were 61.2%, 82.4%, and 56.5% at each checkpoint, respectively, and there were 87.1% (74/85) of patients reporting visual loss in at least one checkpoint. In addition, 76.9% (50/65) of patients could not feel laser flashes during retinal photocoagulation. CONCLUSION: Intraoperative loss of LP under sub-Tenon's anesthesia was a relatively common and reversible event. The conduction block of optic nerve by anesthetic mainly contributed to the visual loss during surgery. Photo-bleaching effect also has some effect on the LP evaluation. Surgeons need to inform and counsel the patients about the intraoperative loss of LP, to prevent any sudden panic attacks in them.

Prolonged ocular exposure leads to retinal lesions in mice.

Retinal lesions in the posterior pole of laboratory mice occur due to native, developmental abnormalities or as a consequence of environmental or experimental conditions. In this study, we investigated the rate and extent of retinal lesions as a result of prolonged ocular exposure following general anesthesia. Following experimental preparation induction procedures (EPIP) involving general anesthesia, mydriasis/cycloplegia, and topical anesthesia to the cornea, two ocular recovery conditions (protected and unprotected) were tested within two different animal recovery chambers (open or closed). The anterior and posterior poles were evaluated for the development of retinal lesions using digital color photography, scanning laser ophthalmoscopy, and spectral-domain optical coherence during anesthesia recovery and up to 2.5 months thereafter. In some mice, electroretinograms, histological and immunohistological evaluations were performed to assess functional and structural changes that accompanied the retinal lesions detected by in vivo imaging. Our data suggests that prolonged ocular surface exposure to circulating ambient room air leads to significant anterior and posterior segment ocular complications. The most abundant, semi-reversible complication observed was the development of lesions in the outer retina, which had a 90% probability of occurring after 45 min of exposure. The lesions mostly resolved short-term, but functional and imaging evidence suggest that some perturbations to the outer retina may persist one or more months following initial development.

Safety and efficacy of combined use of propofol and etomidate for sedation during gastroscopy: Systematic review and meta-analysis.

BACKGROUND: Sedation with etomidate or propofol alone during gastroscopy has many side effects. A systematic review and meta-analysis were conducted to evaluate the safety and efficacy of the combined use of propofol and etomidate for sedation during gastroscopy. METHODS: PubMed, Embase, Medline (via Ovid SP), Cochrane library databases, CINAHL (via EBSCO), China Biology Medicine disc (CBMdisc), Wanfang, VIP, and China National Knowledge Infrastructure (CNKI) databases were systematically searched. We included randomized controlled trials (RCTs) comparing the combined use of propofol and etomidate vs etomidate or propofol alone for sedation during gastroscopy. Data were pooled using the random-effects models or fixed-effect model based on heterogeneity. RESULTS: Fifteen studies with 2973 participants were included in the analysis. Compared to propofol alone, the combined use of propofol and etomidate possibly increased recovery time (SMD = 0.14, 95% CI = 0.04-0.24; P = .005), and the risk for myoclonus (OR = 3.07, 95% CI = 1.73-5.44; P < .001), injection pain, and nausea and vomiting. Furthermore, compared to propofol alone, the combination of propofol and etomidate produced an apparent beneficial effect for mean arterial pressure (MAP) after anesthesia (SMD = 1.32, 95% CI = 0.38-2.26; P = .006), SPO2 after anesthesia (SMD = 0.99, 95% CI = 0.43-1.55; P < .001), apnea or hypoxemia (OR = 0.16, 95% CI = 0.08-0.33; P < .001), injection pain, and body movement. Further, compared to etomidate alone, the combination of propofol and etomidate reduced the risk for myoclonus (OR = 0.15, 95% CI = 0.11-0.22; P < .001), body movement, and nausea and vomiting. CONCLUSION: The combination of propofol and etomidate might increase recovery time vs that associated with propofol, but it had fewer side effects on circulation and respiration in patients undergoing gastroscopy. The combined use of propofol and etomidate can improve and produce an apparent beneficial effect on the adverse effects of propofol or etomidate alone, and it was safer and more effective than propofol or etomidate alone.

Analgesic Effect of Caudal Bupivacaine with or without Clonidine in Pediatric Patient.

BACKGROUND: Caudal analgesia has long been the cornerstone to successful pain management in children undergoing abdominal and lower limb surgeries. Its analgesic duration with single shot injection is however limited. So adjuvants are used with local anesthetics in an attempt to increase the duration of caudal analgesia. This study aims to investigate the duration of analgesia provided by Clonidine when added to caudal Bupivacaine. METHODS: A randomized, double blinded, comparative study was conducted on 64 patients, aged two to seven years, scheduled for unilateral inguinal hernia repair. Patients were randomly allocated into two groups of 32 each, with group A receiving bupivacaine two milligram/kilogram and group B receiving bupivacaine two milligram/kilogram with one microgram/kilogramclonidine, (total volume of injectate was one milliliter/kilogram). Duration of analgesia, hemodynamic response and adverse effects, if any were noted. RESULTS: Mean duration of analgesia in group A was 264.12 ± 68.77 minutes and in group B was 520 ± 57.37 minutes, p-value <0.001.Incidence of vomiting was 9% in group A compared to 6% in group B. CONCLUSIONS: Clonidineas an adjuvant to caudal bupivacaine prolongs the duration of analgesia without increasing the adverse effects.

An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery: The T REX pilot study.

BACKGROUND: Concern over potential neurotoxicity of anesthetics has led to growing interest in prospective clinical trials using potentially less toxic anesthetic regimens, especially for prolonged anesthesia in infants. Preclinical studies suggest that dexmedetomidine may have a reduced neurotoxic profile compared to other conventional anesthetic regimens; however, coadministration with either anesthetic drugs (eg, remifentanil) and/or regional blockade is required to achieve adequate anesthesia for surgery. The feasibility of this pharmacological approach is unknown. The aim of this study was to determine the feasibility of a remifentanil/dexmedetomidine/neuraxial block technique in infants scheduled for surgery lasting longer than 2 hours. METHODS: Sixty infants (age 1-12 months) were enrolled at seven centers over 18 months. A caudal local anesthetic block was placed after induction of anesthesia with sevoflurane. Next, an infusion of dexmedetomidine and remifentanil commenced, and the sevoflurane was discontinued. Three different protocols with escalating doses of dexmedetomidine and remifentanil were used. RESULTS: One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another. The caudal block was unsuccessful in two infants. Of the 56 infants who completed the protocol, 45 (80%) had at least one episode of hypertension (mean arterial pressure >80 mm Hg) and/or movement that required adjusting the anesthesia regimen. In the majority of these cases, the remifentanil and/or dexmedetomidine doses were increased although six infants required rescue 0.3% sevoflurane and one required a propofol bolus. Ten infants had at least one episode of mild hypotension (mean arterial pressure 40-50 mm Hg) and four had at least one episode of moderate hypotension (mean arterial pressure <40 mm Hg). CONCLUSION: A dexmedetomidine/remifentanil neuraxial anesthetic regimen was effective in 87.5% of infants. These findings can be used as a foundation for designing larger trials that assess alternative anesthetic regimens for anesthetic neurotoxicity in infants.

Prospective evaluation of anesthetic protocols during pediatric ophthalmic surgery.

PURPOSE: To date, no protocol of anesthesia for pediatric ophthalmic surgery is unanimously recognized. The primary anesthetic risks are associated with strabismus surgery, including oculocardiac reflex, postoperative nausea and vomiting, and postoperative pain. METHODS: This was a prospective, monocentric, observational study conducted in a tertiary pediatric ophthalmic unit. Our anesthetic protocol for strabismus surgery included postoperative nausea and vomiting prevention using dexamethasone and ondansetron. No drug-based prevention of oculocardiac reflex or local/locoregional anesthesia was employed. RESULTS: A total of 106 pediatric ophthalmic surgeries completed between November 2015 and May 2016 were analyzed. The mean patient age was 4.4 (range: 0.2-7.3, standard deviation: 2.4) years. Ambulatory rate was 90%. Oculocardiac reflex incidence was 65% during strabismus surgery (34/52), 50% during congenital cataract surgery (4/8), 33% during intramuscular injection of botulinum toxin (1/3), and 0% during other procedures. No asystole occurred. Postoperative nausea and vomiting incidence was 9.6% after strabismus surgery (5/52) and 0% following the other procedures. One child was hospitalized for one night because of persistent postoperative nausea and vomiting. Postoperative pain generally occurred early on in the recovery room and was quickly controlled. Its incidence was higher in patients who underwent strabismus surgery (27%) than in those who underwent other procedures (9%). CONCLUSION: Morbidity associated with ophthalmic pediatric surgery is low and predominantly associated with strabismus surgery. The benefit-risk ratio and cost-effectiveness of oculocardiac reflex prevention should be questioned. Our postoperative nausea and vomiting rate is low, thanks to the use of a well-managed multimodal strategy. Early postoperative pain is usually well-treated but could probably be more effectively prevented.

Safety and efficacy of a cardiologist-only approach to deep sedation for electrical cardioversion.

AIMS: Electrical cardioversion is still the preferred method to restore sinus rhythm in patients with atrial fibrillation. The main disadvantage is that electrical cardioversion requires deep sedation, generally administered by anaesthesiologists, for safety concern. An exclusively cardiologic management of deep sedation should have the advantage to reduce resources and time consumed. METHODS: All consecutive patients admitted to our division with persistent atrial fibrillation or atrial flutter to undergo elective electrical cardioversion from June 2002 to December 2016 were included. The sedation protocol was managed only by cardiologists and involved the administration of a 5-mg bolus of midazolam, followed by increasing doses of propofol to achieve the desired sedation level. Exclusion criteria were strictly observed. Complications were recorded. A retrospective analysis on a deidentified database has been performed. RESULTS: A total of 1188 electrical cardioversions were scheduled in our centre. A total of 1195 patients were scheduled in our centre, of whom 1188 met inclusion criteria. Electrical cardioversion was performed in 1073 cases (90.3%). Electrical cardioversion was successful in restoring sinus rhythm in 1030 (96.0%) patients. Immediate recurrence of atrial fibrillation occurred in 89 patients (8.3%). 99/1073 (9.22%) patients underwent trans-oesophagel echocardiography before cardioversion. Deep sedation, according to our protocol, was effective in 100% of cases. Midazolam was administered at a dosage of 5 mg to all patients, while propofol was administered at a dosage ranging from 20 to 80 mg (25.1 ±â€Š11.0 mg SD). No anaesthesia-related complications were observed, neither significant respiratory depression requiring intubation nor anaesthesiologist support. CONCLUSION: The exclusively cardiological procedure of deep sedation seems to be safe and effective.

Efficacy and Safety of EMLA Cream for Pain Control Due to Venipuncture in Infants: A Meta-analysis.

: media-1vid110.1542/5852339542001PEDS-VA_2018-1173Video Abstract CONTEXT: The eutectic mixture of lidocaine (EMLA) cream has been used to reduce the pain during venipuncture in infants. OBJECTIVE: To determine the efficacy and safety of EMLA in infants <3 months of age requiring venipuncture in comparison with nonpharmacological interventions in terms of pain reduction, change in physiologic variables, and methemoglobinemia. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and gray literature were searched from inception to August 2017, without language restrictions. STUDY SELECTION: We selected randomized controlled trials in which researchers compared EMLA with nonpharmacological interventions. DATA EXTRACTION: Two reviewers independently performed abstract screening and full-text review, and extracted the data and assessed the risk of bias. RESULTS: Ten randomized controlled trials (907 infants) were included. EMLA revealed little or no effect in reduction of pain (standardized mean difference: 0.14; 95% confidence interval [CI]: -0.17 to 0.45; 6 trials, n = 742; moderate-quality evidence) when EMLA was compared with sucrose, breastfeeding, or placebo. In comparison with placebo, EMLA revealed a small-to-moderate effect on increasing methemoglobin levels (mean difference: 0.35; 95% CI: 0.04 to 0.66; 2 trials, n = 134; low-quality evidence). There was an increased risk of blanching of the skin in the EMLA group (relative risk: 2.63; 95% CI: 1.58 to 4.38; 2 trials, n = 123; I2 = 84%, very low-quality evidence). LIMITATIONS: Our results may not be applicable to older infants. CONCLUSIONS: EMLA reveals minimal benefits in terms of reduction of pain due to venipuncture procedure in comparison with placebo and no benefit in comparison with sucrose and/or breastfeeding. Moreover, it produced an elevation in methemoglobin levels and skin blanching.

The Effect of Adding Midazolam to Propofol Intravenous Sedation to Suppress Gag Reflex During Dental Treatment.

We retrospectively investigated the efficacy and safety of propofol administration alone and in combination with midazolam for gag reflex suppression during dental treatment under intravenous sedation. We included 56 patients with an overactive gag reflex who were to undergo dental treatment under intravenous sedation. They were divided into propofol (P group, n = 22) and midazolam with propofol (MP group, n = 34) groups. The P group received propofol alone, while the MP group received midazolam (0.04 mg/kg) prior to target-controlled infusion (TCI) of propofol (titrated for adequate sedation). The patients' anesthetic records were evaluated for vital sign changes, adverse cardiovascular or respiratory event frequency, the number of forced treatment interruptions, and the TCI-predicted cerebral propofol concentration at gag reflex suppression (posterior tongue stimulation with a dental mirror). No significant differences were observed between the 2 groups preoperatively. There were no cases of forced interruptions or significant respiratory compromise in either group. Cardiovascular adverse event frequency was lower in the MP group than in the P group (all p < .05). Our results suggest that propofol, when combined with midazolam, minimized cardiovascular effects compared with propofol alone when used to suppress the gag reflex in patients during dental treatment under intravenous sedation.

The effect of sedation with a combination of butorphanol and midazolam on quantitative contrast-enhanced ultrasonography of duodenum in healthy dogs.

Quantitative contrast-enhanced ultrasonography (CEUS) enables non-invasive and objective evaluation of intestinal perfusion by quantifying the intensity of enhancement on the intestine after microbubble contrast administration. During CEUS scanning, sedation is sometimes necessary to maintain animal cooperation. Nevertheless, the effect of sedative administration on the canine intestinal CEUS is unknown. This study aimed to investigate the effect of sedation with a combination of butorphanol and midazolam on the duodenal CEUS-derived perfusion parameters of healthy dogs. For this purpose, duodenum was imaged following contrast administration (Sonazoid®, 0.01 ml/kg) in six healthy beagles before and after intravenous injection of a combination of butorphanol (0.2 mg/kg) and midazolam (0.1 mg/kg). Furthermore, hemodynamic parameters including blood pressure and heart rate were recorded during the procedure. Five CEUS derived perfusion parameters including time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), wash-in and wash-out rates (WiR and WoR, respectively) before and after sedation were statistically compared. The result showed that no significant change was detected in any of perfusion parameters. Systolic and mean arterial pressures significantly reduced after sedative administration, but diastolic arterial pressure and heart rate did not significantly change. Moreover, no significant partial correlation was observed between perfusion parameters and hemodynamic parameters. Thus, we concluded that the combination did not cause significant influence in duodenal CEUS perfusion parameters and could be a good option for sedation prior to duodenal CEUS in debilitated dogs.

Comparison of DNA Damage and Oxidative Stress in Patients Anesthetized With Desflurane Associated or Not With Nitrous Oxide: A Prospective Randomized Clinical Trial.

BACKGROUND: Little is known about the effects of desflurane associated or not with nitrous oxide (N2O) on oxidative stress and patient genetic material. The aim of this study was to compare the effects of anesthesia maintained with desflurane associated or not with N2O on DNA damage (as a primary outcome) and oxidative stress (as a secondary outcome) in patients who underwent an elective minimally invasive surgery. METHODS: This prospective randomized clinical trial analyzed 40 patients of both sexes with an American Society of Anesthesiologists physical status I who were 18-50 years of age and scheduled for septoplasty. The patients were randomly allocated into 2 groups according to anesthesia maintenance as follows: desflurane (n = 20) or desflurane/N2O (n = 20). Blood samples were collected before anesthesia (T1 = baseline), 1.5 hours after anesthesia induction (T2), and on the morning of the postoperative first day (T3). Basal and oxidative DNA damage (determined using formamidopyrimidine DNA glycosylase to detect oxidized purines and endonuclease III to detect oxidized pyrimidines) were evaluated using the comet assay. Oxidative stress markers were evaluated based on lipid peroxidation (by assessing 4-hydroxynonenal and 8-iso-prostaglandin F2α [8-isoprostane] using enzyme linked immunosorbent immunoassay), protein carbonyls (assessed by enzyme linked immunosorbent immunoassay), and antioxidant defense (ferric-reducing antioxidant power by spectrophotometry). The effect size was expressed as the mean differences between groups and the corresponding 95% confidence interval (CI). RESULTS: There was no significant mean difference between groups in relation to DNA damage (-1.7 [95% CI, -7.0 to 3.5]), oxidized DNA pyrimidines (-1.8 [95% CI, -12.5 to 8.9]) and purines (-1.9 [95% CI, -13.9 to 10.1]), 4-hydroxynonenal (-0.2 [95% CI, -2.8 to 2.4]), 8-isoprostane (549 [95% CI, -2378 to 3476]), protein carbonyls (0.2 [95% CI, -2.1 to 2.3]), or ferric-reducing antioxidant power (24 [95% CI, -52.0 to 117.2]). CONCLUSIONS: The coadministration of 60% N2O with desflurane did not seem to impair the effects on DNA or the redox status compared with desflurane anesthesia, suggesting that both studied anesthetic techniques can be suitable options for healthy individuals who undergo minimally invasive surgery lasting at least 1.5 hours. However, due to the low power of the study, more research is necessary to confirm our findings.

Sufentanil-medetomidine anaesthesia compared with fentanyl/fluanisone-midazolam is associated with fewer ventricular arrhythmias and death during experimental myocardial infarction in rats and limits infarct size following reperfusion.

To improve infarct healing following myocardial infarction in humans, therapeutic interventions can be applied during the inflammatory response. Animal models are widely used to study this process. However, induction of MI in rodents is associated with high mortality due to ventricular fibrillation (VF) during coronary artery ligation. The anaesthetic agent used during the procedure appears to influence the frequency of this complication. In this retrospective study, the effect on ventricular arrhythmia incidence during ligation and infarct size following in vivo reperfusion of two anaesthetic regimens, sufentanil-medetomidine (SM) and fentanyl/fluanisone-midazolam (FFM) was evaluated in rats. Anaesthetics were administered subcutaneously using fentanyl/fluanisone (0.5 mL/kg) with midazolam (5 mg/kg) (FFM group, n = 48) or sufentanil (0.05 mg/kg) with medetomidine (0.15 mg/kg) (SM group, n = 47). The coronary artery was ligated for 40 min to induce MI. Heart rate and ventricular arrhythmias were recorded during ligation, and infarct size was measured via histochemistry after three days of reperfusion. In the SM group, heart rate and VF incidence were lower throughout the experiment compared with the FFM group (6% versus 30%) ( P < 0.01). Fatal VF did not occur in the SM group whereas this occurred in 25% of the animals in the FFM group. Additionally, after three days of reperfusion, the infarcted area following SM anaesthesia was less than half as large as that following FFM anaesthesia (8.5 ± 6.4% versus 20.7 ± 5.6%) ( P < 0.01). Therefore, to minimize the possibility of complications related to VF and acute death arising during ligation, SM anaesthesia is recommended for experimental MI in rats.

Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

OBJECTIVE: To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. STUDY DESIGN: Prospective, blinded, randomized, experimental study. ANIMALS: A group of 12 intact female dogs. METHODS: Following intramuscular dexmedetomidine (10 µg kg-1) and methadone (0.1 mg kg-1) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg-1) (group AP) or alfaxalone (2 mg kg-1) preceded by fentanyl (2 µg kg-1) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg-1 minute-1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 µg kg-1 hour-1) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). RESULTS: The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg-1 minute-1 (group AP) versus 0.13 ± 0.01 mg kg-1 minute-1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor.

Postinduction apnoea in dogs premedicated with acepromazine or dexmedetomidine and anaesthetized with alfaxalone or propofol.

OBJECTIVE: To compare incidence and duration of postinduction apnoea in dogs after premedication with methadone and acepromazine (MA) or methadone and dexmedetomidine (MD) followed by induction with propofol (P) or alfaxalone (A). STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: A total of 32 American Society of Anesthesiologists class I dogs (15 females, 17 males), aged between 4 months and 4 years, weighing between 3 and 46 kg. METHODS: Dogs were randomly allocated to be administered MA+P, MA+A, MD+P or MD+A (methadone 0.5 mg kg-1 and acepromazine 0.05 mg kg-1 or dexmedetomidine 5 µg kg-1). Induction agents were administered intravenously via syringe driver (P at 4 mg kg-1 minute-1 or A at 2 mg kg-1 minute-1) until successful endotracheal intubation and the endotracheal tube connected to a circle system with oxygen flow at 2 L minute-1. Oxygen saturation of haemoglobin (SpO2), end tidal partial pressure of carbon dioxide and respiratory rate were monitored continuously. If apnoea (≥ 30 seconds without breathing) occurred, the duration until first spontaneous breath was measured. If SpO2 decreased below 90% the experiment was stopped and manual ventilation initiated. Data were analysed with general linear models with significance set at p ≤ 0.05. RESULTS: There was no statistical difference in the incidence (11 of 16 dogs in A groups and 12 of 16 dogs in P groups), or mean ± standard deviation duration (A groups 125 ± 113 seconds, P groups 119 ± 109 seconds) of apnoea. The SpO2 of one dog in the MD+P group decreased below 90% during the apnoeic period. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol and alfaxalone both cause postinduction apnoea and the incidence and duration of apnoea is not influenced by the use of acepromazine or dexmedetomidine in premedication. Monitoring of respiration is recommended when using these premedication and induction agent combinations.

Pharmacological properties of various anesthetic protocols in 10-day-old neonatal rats.

In general, the anesthesia in neonates involves high risk. Although hypothermic anesthesia is recommended in rats up to the age of 7 days, neonatal anesthesia for later periods has not been standardized. The present study investigated the pharmacological properties of conventional anesthetic protocols in 10-day-old SD rats. The rats were anesthetized with four anesthetics: a combination of ketamine and xylazine (K/X); a combination of medetomidine, midazolam, and butorphanol (M/M/B); isoflurane; and sevoflurane. Anesthetic depth was scored by reflex response to noxious stimuli. Induction and recovery times were recorded. Vital signs and mortality rate were evaluated for safety assessment. All rats died after administration of K/X at a dose of 60/6 mg/kg, whereas K/X at 40/4 mg/kg resulted in insufficient anesthetic depth, indicating inappropriate for neonatal anesthesia. Although M/M/B at the adult rat dose (0.15/2/2.5 mg/kg) did not provide surgical anesthetic depth, the mouse dose (0.3/4/5 mg/kg) showed sufficient anesthetic depth with relatively stable vital signs. Isoflurane required a long induction period, and caused remarkable respiratory depression and hypothermia, resulted in a 25% mortality rate. In contrast, sevoflurane provided consistent surgical anesthetic depth with rapid induction. Although respiratory rate decrease was markedly observed, all rats survived. Among the anesthetic protocols investigated in the present study, sevoflurane and M/M/B at the mouse dose were recommended for the neonatal anesthesia. Compared with adult rats, the required dose of both anesthetics in neonates was higher, possibly associated with their lower anesthetic sensitivity.