Intensive Sedation Research Articles

Intraoperative local infiltration with ropivacaine 0.5% in women undergoing vaginal hysterectomy and pelvic floor repair: Randomized double-blind placebo-controlled trial

ObjectiveTo evaluate the effectiveness of infiltration with ropivacaine 0.5% on controlling postoperative pain in women undergoing vaginal hysterectomy (VH) and pelvic floor repair for prolapse stage > II. Study designThis double-blind randomized 1:1 placebo-controlled trial included 59 women. Thirty millilitres of ropivacaine 0.5% or placebo was infiltrated in the round and uterosacral ligaments and in the perineal body. Primary outcomes included postoperative pain intensity at rest and during cough (measured using 10-cm visual analogue scale), and proportion of patients reporting moderate/severe pain. Secondary outcomes included morphine consumption and assessment of nausea, vomiting and sedation. Outcomes were compared between groups at 2, 4, 8 and 24 h postoperatively. Statistical (p-values) and clinical significance {effect size [Cliff’s delta] [95% confidence interval (CI)] and odds ratio (95% CI)} of results were assessed. Outcomes are presented as median (min–max) and n (%). ResultsPain intensity was lower after ropivacaine infiltration compared with placebo at 2 and 4 h postoperatively at rest [0.5 (0.1–7.2) vs 1.1 (0.2–9.3) (p = 0.007) and 1.3 (0.1–5.1) vs 3.1 (0.1–9.8) (p = 0.02), respectively] and during cough [0.9 (0.1–8.9) vs 1.9 (0.1–10) (p = 0.03) and 1.6 (0.1–4.7) vs 3.2 (0.3–9.6) (p = 0.009), respectively]. The proportion of patients with moderate/severe pain was significantly less after ropivacaine infiltration compared with placebo at 2, 4 and 8 h postoperatively at rest [4% vs 32% (p = 0.03), 16% vs 44% (p = 0.03) and 12% vs 40% (p = 0.02), respectively] and during cough [8% vs 40% (p = 0.008), 16% vs 52% (p = 0.007) and 20% vs 52% (p = 0.02), respectively]. Patients in the ropivacaine group consumed significantly less morphine compared with those in the placebo group up to 24 h postoperatively [4 (0–17) mg vs 7 (0–19) mg (p = 0.02)]. The incidence of nausea and vomiting was 3 (12%) and 0–2 (0–8%) in the ropivacaine group, compared with 1–7 (4–28%) and 1–4 (4–16%) in the placebo group. No significant difference was found in the proportion of patients using morphine, proportion of patients reporting the presence of nausea/vomiting, and the intensity of sedation between the groups (all p > 0.05). ConclusionLocal infiltration with ropivacaine 0.5% significantly reduces postoperative pain and morphine consumption in patients undergoing VH and pelvic floor repair for advanced pelvic organ prolapse.

General anesthesia in Sapajus nigritus (black capuchin)

Background: The black capuccin (Sapajus nigritus) is one of the most abundant primate specimens in Brazil. Among population control techniques, vasectomy can be used once it maintains the animal's leading behavior in the group through hormonal presence, production of spermatogenic series, and copula. However, due to their escape behavior, agitation, in addition to the impossibility of knowing the physiological state of these animals beforehand, their capture poses a considerable challenge. Thus, chemical restraint is indispensable and the use of effective and safe anesthetic protocols to animal integrity is of paramount importance. In this scenario, the present study aims to report the anesthesia of a black capuccin submitted to vasectomy.Case: A 1-year-old male, 1.1 kg monkey (Sapajus nigritus) was admitted at a Veterinary Hospital after being found on the ground in a natural reserve in the town of Assis Chateaubriand, in the west of Parana State. After clinical evaluation, the patient was submitted to vasectomy as a birth control method, before his return to the natural area, which presented overpopulation of the species. After preanesthetic examinations, the animal was considered healthy, and thus, premedicated with the combination of dexmedetomidine (10 μg/kg) and ketamine (10 mg/kg), intramuscularly. Anesthetic induction with propofol was performed to effect. Laringeal desensitization was achieved with 2% lidocaine (2 mg/kg), which allowed orotracheal intubation through direct visualization. Anesthesia was maintained with 1% isoflurane in a 0.5 oxygen fraction and spontaneous ventilation using a non-rebreathing circuit. The spermatic cord and the skin were desensitized with lidocaine (2 mg/kg). During the procedure, the animal was monitored for pulse oximetry, electrocardiogram, systolic blood pressure, body temperature, end tidal CO2 (ETCO2), and end tidal isoflurane. The animal also received 10 mL/kg/h ringer lactate throughout anesthesia and 30 mg/kg ampiciline as prophylactic antibiotic. After the completion of the surgery, inhalation anesthesia was interrupted and the animal was allowed to wake up. Discussion: The combination of 10 µg/kg dexmedetomidine and 10 mg/kg ketamine caused intense muscle relaxation and short-term sedation, which lasted 15 min. Protocol was sufficient for veno puncture and pre-oxygenation, but doses should be increased for longer procedures. Although other authors reported physiologic alterations with higher doses of these drugs, such complications were not observed in the present case. The anesthetic induction was smooth, with no excitement or complications. Propofol was infused at 1 mg/10 s, and a total dose of 10 mg/kg was necessary for induction. This rapid infusion rate could have caused the increase in propofol total dose, as described elsewhere. Propofol and local lidocaine allowed orotracheal intubation with a 2.5 mm uncuffed neonatal tube. During surgery, analgesia was achieved with pre surgical local anesthetic and a single bolus of fentanyl during duct deferens manipulation. During anesthesia, heart rate was maintained between 140 and 170 bpm; systolic blood pressure, between 85 and 110 mmHg; respiratory rate, between 30 and 50 mpm; and ETCO2, between 25 and 30 mmHg. No assistance in ventilation was necessary. The procedure lasted one hour, and extubation occurred seven minutes after the interruption of inhalational anesthetic. Anesthesia and anesthesia recovery occurred without complications, allowing the accomplishment of a short duration surgical procedure. After the post operatory period, the animal was reintroduced to the wild, with authorization of the state environmental agency. In conclusion, low dose dexmedetomidine combined with ketamine is adequate for rapid chemical restraint of black capuccin, and do not cause physiologic alterations during isoflurane anesthesia.

Different Analgesic Routes of Magnesium Sulfate: Intravenous versus Pectoralis II Interfascial Plane Block for Breast Cosmetic Surgeries.

Purpose:The purpose of the study is to evaluate the most effective analgesic route of magnesium sulfate (MgSO4) either intravenous (i.v.) or pectoralis interfascial plane block.Patients and Methods:Fifty adult female patients were divided into two equal groups: i.v. MgSO4 and Pecs II block MgSO4 (Pecs MgSO4) group. After general anesthesia, in i.v. MgSO4 group, the local anesthetic (LA) for Pecs II block was prepared by adding 3 mL saline to 57 mL bupivacaine 0.25% divided equally for each side. A bolus i.v. solution of MgSO4 10% 0.5 mL.kg-1 diluted in saline in a total volume of 100 mL was given over 15 minutes. Then, the solution for continuous i.v. infusion; 30 mL MgSO4 10% and 70 mL saline was infused at the rate of 0.5 mL.kg-1.h-1 intraoperatively. For PecsMgSO4 group, LA formed of 3 mL MgSO4 10% added to 57 mL bupivacaine 0.25%. Whereas, 100 mL saline was given as bolus i.v. followed by continuous infusion of 100 mL normal saline at the rate of 0.5 mL.kg-1.h-1.Results:In the group received MgSO4-bupivacaine Pecs II block, there was a nonsignificant decrease in postoperative morphine consumption compared to i.v. administration of MgSO4. The two groups were comparable in the intensity of pain and sedation scores.Conclusion:The use of bupivacaine Pecs II block enhanced with addition of MgSO4 to pectoralis interfascial plane block or intravenously in patients underwent breast cosmetic surgeries under general anesthesia was associated with comparable results of the postoperative morphine requirements, intensity of postoperative pain, and extension of the duration of postoperative analgesia. The intraoperative hemodynamic effects i.v. MgSO4 were superior to the pectoralis interfascial plane route of administration.

A Novel Research Method for Determining Sedative Exposure in Critically Ill Patients.

Although potent sedative and opioid drugs are some of the most commonly used medications to manage pain, anxiety, and discomfort in critically ill patients, conducting clinical trials where sedative and opioid medications are outcome variables within a longitudinal research design can be a methodological challenge. The purpose of this article is to provide in detail a conceptual discussion of the concept and analysis of sedative exposure: A novel research analysis method for aggregating sedative and opioid medication doses from disparate drug classes commonly administered to critically ill patients and used by our team in several clinical research studies. Comparing the dose of each sedative and opioid administered to an individual patient (within a defined time interval) to all other patients in a research study receiving the same medications allows for ranking of dosages for each medication by quartiles. Rank values for all sedatives and opioids received can be summed to a single value resulting in a Sedation Intensity Score. In addition, a simple count of how many hours at least one dose of a sedative or opioid medication has been administered can determine sedation frequency. This method can allow for comparison of sedative exposure with medications from disparate drug classes and for analysis of estimates of change in medication use over time. This novel research analysis method can overcome the challenges and limitations of determining changes in sedative and opioid medication regimens in cohort and clinical trial study designs.

Sedation Intensity in the First 48 hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study: Shehabi Y, Bellomo R, Kadiman S, et al. Crit Care Med. 2018;46:850-859

Sedation Intensity in the First 48 hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study: Shehabi Y, Bellomo R, Kadiman S, et al. Crit Care Med. 2018;46:850-859

Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study*

In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Harmonized data from prospective multicenter international longitudinal cohort studies SETTING:: Diverse mix of ICUs. Critically ill patients expected to be ventilated for longer than 24 hours. Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (SD) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47-8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15-1.46]; p < 0.001, delirium hazard ratio [95% CI], 1.25 [1.10-1.43]), p value equals to 0.001 and reduced chance of early extubation hazard ratio (95% CI) 0.80 (0.73-0.87), p value of less than 0.001. Agitation level independently predicted subsequent delirium hazard ratio [95% CI], of 1.25 (1.04-1.49), p value equals to 0.02. Delirium or mobilization episodes within 168 hours, adjusted for sedation intensity, were not associated with survival. Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation. These observations suggest that keeping sedation level equivalent to a Richmond Agitation Sedation Scale 0 is a clinically desirable goal.

PL03: Prophylactic administration of diphenhydramine to reduce neuroleptic side-effects in the acute care setting: a systematic review and meta-analysis

Introduction: Neuroleptics are commonly used drugs to treat different conditions (e.g. psychosis, migraines) in the acute care setting and the emergency department. Their side effects can be disabling or, worse, fatal. The use of diphenhydramine to prevent those side-effects is widespread, but remains controversial. We performed a systematic review to determine if prophylactic administration of diphenhydramine (PAD) reduces the incidence of neuroleptic side-effects. Methods: Data sources: Medline, Embase, Cochrane Library, PsycInfo and Web of Science were searched. References from reviews that were identified in the search and from included studied were also reviewed for inclusion. Study selection: Randomized controlled trials evaluating any neuroleptic with PAD versus the same neuroleptic alone or with any inactive agent. Primary outcome was incidence of any extra-pyramidal side-effect. Secondary outcomes were akathisia, usage of rescue medication, subjective restlessness, neuroleptic malignant syndrome, sedation and sedation intensity. Data extraction: Independent reviewers scanned identified citations, extracted data and assessed for risk of bias. Data analysis: Meta-analysis was performed using random effect models. Heterogeneity and quality of evidence were assessed using, respectively, I2 and the GRADE approach. Results: Results: Of 1566 identified citations, nine studies (n=1436) met all eligibility criteria. Four studies were specifically designed to assess for neuroleptic side-effects. Four studies were at high risk of bias. In primary analysis, PAD had no effect on the incidence of extra-pyramidal symptoms (7 studies, n=1393 patients, RR 0.70 [0.40-1.22]), akathisia (5 studies, n=1094 patients, RR 0.81 [0.36-1.82]) and sedation (5 studies; n=1079, RR 1,48 [0.90-2.42]). Higher dosage of diphenhydramine was not associated with a greater reduction of extra-pyramidal side-effects. In a sensitivity analysis excluding an outlier study (n=120, RR 6.63 [1.55-28,35]), PAD was associated with a significant decrease in extra-pyramidal side-effects (6 studies, n=1273, RR 0.56 [0,38-0.82]), but not with any of the secondary outcome measures. Conclusion: Conclusion: When excluding an outlier study, PAD was associated with a significant reduction of extra-pyramidal side-effects. However, PAD did not significantly influence the incidence of akathisia. Overall quality of evidence is low. Further studies are warranted. PAD represents an interesting treatment option against neuroleptic side-effects, but its widespread usage whitout strong evidence to support it raises concerns.

Gamma-aminobutyric acid agonists for antipsychotic-induced tardive dyskinesia.

Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD. 1. Primary objectiveThe primary objective was to determine whether using non-benzodiazepine GABA agonist drugs for at least six weeks was clinically effective for the treatment of antipsychotic-induced TD in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses.2. Secondary objectivesThe secondary objectives were as follows.To examine whether any improvement occurred with short periods of intervention (less than six weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.To examine whether there was a differential effect between the various compounds.To test the hypothesis that GABA agonist drugs are most effective for a younger age group (less than 40 years old). We searched the Cochrane Schizophrenia Group Trials Register (last searched April 2017), inspected references of all identified studies for further trials, and, when necessary, contacted authors of trials for additional information. We included randomised controlled trials of non-benzodiazepine GABA agonist drugs in people with antipsychotic-induced TD and schizophrenia or other chronic mental illness. Two review authors independently selected and critically appraised studies, extracted and analysed data on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous data we calculated mean differences (MD). We assumed that people who left early had no improvement. We contacted investigators to obtain missing information. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We included 11 studies that randomised 343 people. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, participants and outcome assessors were not clearly blinded. For some studies we were unsure if data were complete, and data were often poorly or selectively reported.Data from six trials showed that there may be a clinically important improvement in TD symptoms after GABA agonist treatment compared with placebo at six to eight weeks follow-up (6 RCTs, n = 258, RR 0.83, CI 0.74 to 0.92; low-quality evidence). Data from five studies showed no difference between GABA agonist treatment and placebo for deterioration of TD symptoms (5 RCTs, n = 136, RR 1.90, CI 0.70 to 5.16; very low-quality evidence). Studies reporting adverse events found a significant effect favouring placebo compared with baclofen, sodium valproate or progabide for dizziness/confusion (3 RCTs, n = 62 RR 4.54, CI 1.14 to 18.11; very low-quality evidence) and sedation/drowsiness (4 RCTS, n = 144, RR 2.29, CI 1.08 to 4.86; very low-quality evidence). Studies reporting on akathisia (RR 1.05, CI 0.32 to 3.49, 2 RCTs, 80 participants), ataxia (RR 3.25, CI 0.36 to 29.73, 2 RCTs, 95 participants), nausea/vomiting (RR 2.61, CI 0.79 to 8.67, 2 RCTs, 64 participants), loss of muscle tone (RR 3.00, CI 0.15 to 59.89, 1 RCT, 10 participants), seizures (RR 3.00, CI 0.24 to 37.67, 1 RCT, 2 participants), hypotension (RR 3.04, CI 0.33 to 28.31, 2 RCTs, 119 participants) found no significant difference between GABA drug and placebo (very low-quality evidence). Evidence on mental state also showed no effect between treatment groups (6 RCTS, n = 121, RR 2.65, CI 0.71 to 9.86; very low-quality evidence) as did data for leaving the study early (around 10% in both groups, 6 RCTS, n = 218, RR 1.47, CI 0.69 to 3.15; very low-quality evidence). No study reported on social confidence, social inclusion, social networks, or personalised quality of life, a group of outcomes selected as being of particular importance to patients. We are uncertain about the evidence of the effects of baclofen, progabide, sodium valproate or tetrahydroisoxazolopyridinol (THIP) for people with antipsychotic-induced TD. Evidence is inconclusive and unconvincing. The quality of data available for main outcomes ranges from very low to low. Any possible benefits are likely to be outweighed by the adverse effects associated with their use.

Effects of Three Acepromazine Doses on the Incidence of Morphine-Induced Vomiting, Sedation and Some Physiological Variables in Dogs

Background: Acepromazine was found to reduce the incidence of vomiting induced by opioids such as morphine, hydromorphone and oxymorphone in dogs. Despite the effectiveness of the phenothiazine in preventing opioid-induced vomiting in this species, a single dose of acepromazine (0.05 mg/kg) was tested and the influence of dose on the antiemetic effect of the drug is unknown. The primary objective of this study was to evaluate the effect of three acepromazine doses on the incidence of vomiting induced by morphine in dogs. A secondary aim was to assess the degree of sedation and effects on physiological variables following administration of the combinations tested.Materials, Methods &amp; Results: All dogs received 0.5 mg/kg morphine (IM). Fifteen min before morphine, dogs in the Control, ACPLD, ACPMD and ACPHD groups were administered (IM) physiological saline or acepromazine at doses of 0.025, 0.05 and 0.1 mg/kg, respectively. In Phase 1, purpose-bred dogs (n = 8) underwent each of the four treatments in a randomized, crossover design; the incidence of vomiting, sedation, pulse rate (PR), systolic, mean and diastolic blood pressures (SAP, MAP and DAP) were investigated for 60 min. Sedation was assessed by a numeric descriptive scale (NDS, range 0-3) and a simple numerical scale (SNS, range 1-10). In Phase 2, client-owned dogs (n = 50) received a single treatment and only the incidence of vomiting was assessed. There was no significant difference between groups on the incidence of vomiting recorded in Phase 1, Phase 2 and the average of Phases 1 and 2. A significant decrease in PR was observed in most groups but no significant difference was detected between groups. Blood pressure decreased in all groups; during most of the evaluation period, SAP, MAP and DAP were significantly higher in the Control than in other treatments. Dogs in this study presented mild to intense sedation. A significant difference in NDS scores was observed between the Control and ACPMD groups whereas for SNS scores, significant differences were detected between the ACPMD and ACPHD groups compared with the Control group. The number of dogs presenting intense sedation as judged by the NDS (NDS score = 3) were: 1/8, 3/8, 3/8 and 4/8 dogs in the Control, ACPLD, ACPMD and ACPHD groups, respectively.Discussion: The hypothesis of the study was rejected. The acepromazine dose did not influence the frequency of morphineinduced vomiting, the degree of sedation or cardiovascular variables after administration of either treatment. The frequency of vomiting was high (≥ 75%) in dogs of the present study regardless of the treatment administered. There was no significant difference in the frequency of vomiting in ACPLD, ACPMD and ACPHD as compared to the Control group. This finding was unexpected because it has been reported in a previous study that acepromazine reduced the incidence of opioid-induced vomiting in dogs. ACPLD, ACPMD and ACPHD improved the quality of sedation compared to the Control treatment but no significant difference in sedation scores was observed among these groups. These findings suggest that, when combined to morphine, there is no improvement in sedation when the acepromazine dose is increased above 0.025 mg/kg in dogs. Despite a significant decrease, mean values of PR, SAP, MAP and DAP remained within the physiological range for conscious dogs. In summary, none of the acepromazine doses was effective in preventing morphine-induced vomiting in dogs. Sedation is greater after acepromazine-morphine combinations than after morphine alone and is not influenced by the acepromazine dose. Cardiovascular effects induced by combinations administered in this study were well tolerated and of little clinical relevance to healthy conscious dogs.

The SPICE III study protocol and analysis plan: a randomised trial of early goaldirected sedation compared with standard care in mechanically ventilated patients.

Sedation strategy in critically ill patients who are mechanically ventilated is influenced by patient-related factors, choice of sedative agent and the intensity or depth of sedation prescribed. The impact of sedation strategy on outcome, in particular when delivered early after initiation of mechanical ventilation, is uncertain. To present the protocol and analysis plan of a large randomised clinical trial investigating the effect of a sedation strategy, in critically ill patients who are mechanically ventilated, based on a protocol targeting light sedation using dexmedetomidine as the primary sedative, termed "early goal-directed sedation", compared with usual practice. This is a multinational randomised clinical trial in adult intensive care patients expected to require mechanical ventilation for longer than 24 hours. The main exclusion criteria include suspected or proven primary brain pathology or having already been intubated or sedated in an intensive care unit for longer than 12 hours. Randomisation occurs via a secured website with baseline stratification by site and suspected or proven sepsis. The primary outcome is 90-day all-cause mortality. Secondary outcomes include death, institutional dependency, cognitive function and health-related quality of life 180 days after randomisation, as well as deliriumfree, coma-free and ventilation-free days at 28 days after randomisation. A predefined subgroup analysis will also be conducted. Analyses will be on an intention-to-treat basis and in accordance with this pre-specified analysis plan. SPICE III is an ongoing large scale clinical trial. Once completed, it will inform sedation practice in critically ill patients who are ventilated.

Predictive Associations of Music, Anxiety, and Sedative Exposure on Mechanical Ventilation Weaning Trials.

Weaning from mechanical ventilation requires increased respiratory effort, which can heighten anxiety and later prolong the need for mechanical ventilation. To examine the predictive associations of music intervention, anxiety, sedative exposure, and patients' characteristics on time to initiation and duration of weaning trials of patients receiving mechanical ventilation. A descriptive, correlational design was used for a secondary analysis of data from a randomized trial. Music listening was defined as self-initiated, patient-directed music via headphones. Anxiety was measured daily with a visual analog scale. Sedative exposure was operationalized as a daily sedation intensity score and a sedative dose frequency. Analyses consisted of descriptive statistics, graphing, survival analysis, Cox proportional hazards regression, and linear regression. Of 307 patients, 52% were women and 86% were white. Mean age was 59.3 (SD, 14.4) years, mean Acute Physiology and Chronic Health Evaluation III score was 62.9 (SD, 21.6), mean duration of ventilatory support was 8 (range, 1-52) days, and mean stay in the intensive care unit was 18 (range, 2-71) days. Music listening, anxiety levels, and sedative exposure did not influence time to initial weaning trial or duration of trials. Clinical factors of illness severity, days of weaning trials, and tracheostomy placement influenced weaning patterns in this sample. Prospective studies of music intervention and other psychophysiological factors during weaning from mechanical ventilation are needed to better understand factors that promote successful weaning.

Effect of Epidural Dexmedetomidine Combined With Ropivacaine in Labor Analgesia: A Randomized Double-Blinded Controlled Study.

The purpose of our study is to evaluate the effect of adding dexmedetomidine to epidural ropivacaine in patients undergoing labor epidural analgesia. Eighty healthy women were randomly assigned to 2 groups: control group (R; n=40) received epidural 0.125% ropivacaine for labor analgesia, whereas the study group (D; n=40) received epidural 0.125% ropivacaine with dexmedetomidine in addition. The blood pressure, heart rate, and the severity of pain of the parturient was assessed, the duration of the first stage and the second stage of labor time, the rate of instrumental delivery and the rate of cesarean section were recorded. The side effects (nausea and vomiting), intensity of maternal sedation, and neonatal Apgar scores were also recorded. The visual analog scales, systolic blood pressure, diastolic blood pressure, and heart rates of D group were significant lower than that of R group at most time intervals after epidural analgesia. The duration of the first and second stage of labor, the rate of instrumental delivery and cesarean section, neonatal 1- and 5-minute Apgar scores, umbilical artery pH, maternal motor blockade scores, intensity of maternal sedation, and the incidence of maternal complications did not show significant difference between 2 groups. Low concentration of epidural ropivacaine (0.125%) combined with dexmedetomidine (0.5 μg/kg) reduces the feeling of pain, and does not show the problems of motor blockage, hemodynamic instability, extension of production process, and complications such as nausea and vomiting. Our study was registered with Chinese Clinical Trial Registry (ChiCTR-IOR-15007263).

Effects of three methadone doses combined with acepromazine on sedation and some cardiopulmonary variables in dogs

ObjectiveTo evaluate the sedative and cardiopulmonary effects of three methadone doses, combined with acepromazine, in dogs. Study designProspective, randomized, complete block study. AnimalsSix healthy, adult, cross-bred dogs weighing 17.2±4.4 kg (mean±standard deviation). MethodsEach dog was administered four treatments: acepromazine (0.05 mg kg−1) alone or acepromazine (same dose) in combination with methadone (0.25, 0.50 or 0.75 mg kg−1). All drugs were administered intramuscularly. Sedation was scored by a numeric descriptive scale (NDS, range 0–3) and a simple numerical scale (SNS, range 0–10). Heart rate, invasive blood pressure, arterial blood gases and rectal temperature were measured at 15 to 30 minute intervals for 120 minutes. ResultsAccording to NDS scores, mild to moderate sedation (NDS=1–2) was observed in most dogs in the acepromazine treatment, with only one out of six dogs scored as exhibiting intense sedation (NDS=3). All treatments with methadone resulted in significantly higher SNS scores compared with acepromazine alone. In these treatments, most dogs exhibited intense sedation (NDS=3). Increasing the dose of methadone from 0.25 to 0.50 or 0.75 mg kg−1 prolonged sedation in a dose-related manner, but did not influence the degree of sedation. The main adverse effects following administration of acepromazine–methadone treatments were decreased blood pressure, mild respiratory acidosis and decreased rectal temperature. These effects were well tolerated and resolved without treatment. Conclusions and clinical relevanceIn this study in six dogs, acepromazine–methadone administration resulted in intense sedation in most dogs. The results are interpreted to indicate that a low dose of methadone (0.25 mg kg−1) administered in combination with acepromazine (0.05 mg kg−1) will induce short-term sedation in dogs, whereas higher doses of methadone should be administered when prolonged sedation is desired.

Randomized controlled comparative trial between low dose dexmedetomidine sedation and that of fentanyl in children after surgical procedures in surgical Pediatric Intensive Care Unit

BackgroundChildren undergoing different surgical procedures and requiring postoperative ventilation need intense analgesia and sedation. This was done using opioids and benzodiazepines with their common side effects as respiratory depression and prolonged sedation.Aim of the studyTo study the efficacy of sedation and time taken form stopping the infusion to extubation using low dose of dexmedetomidine compared with fentanyl sedation in post-operative Pediatric surgical Intensive Care Unit (PICU).Patients and MethodsA randomized double-blind study involving 50 children undergoing different surgical procedures was performed. The patients were equally divided into two groups, each including 25 patients. One group sedated with fentanyl at 1 μg/kg/h (Fen Group) and the other group sedated with dexmedetomidine at 0.3 μg/kg/h (Dex Group) for 18 h post-operatively with intermittent rescue fentanyl 0.5 μg/kg bolus in the 2 groups as required during endotracheal suctioning. The depth of sedation was assessed using the Ramsay sedation score, the tracheal suctioning score and pediatric intensive care unit sedation score. The time taken from discontinuation of infusion till extubation was recorded.ResultsAll sedation scores in the fentanyl and dexmedetomidine groups were comparable. Hemodynamic parameters were comparable between the two groups. Average time (in minutes) required for extubation after stopping the infusions was 136.2 (±54.2 SD) in the Dex group compared with 341.4 (±125.4 SD) in the Fen group. The difference in mean time for extubation was statistically significant. Conclusions: Low dose dexmedetomidine provides adequate sedation for mechanically ventilated children and also early extubation as compared with fentanyl.

Is there a role for music in the ICU?

Results Patients in the PDM group listened to music for a mean of 79.8 (median (range) 12 (0 to 796)) minutes/day. Patients in the NCH group wore the noise-abating headphones for a mean of 34.0 (median (range), 0 (0 to 916)) minutes/day. The mixed-models analysis showed that, at any time point, patients in the PDM group had an anxiety score that was 19.5 points lower (95% confidence interval, �32.2 to �6.8) than patients in the usual care group (P = 0.003). By the fifth study day, anxiety was reduced by 36.5% in PDM patients. The treatment × time interaction showed that PDM significantly reduced both measures of sedative exposure. Compared with usual care, the PDM group had reduced sedation intensity by �0.18 (95% confidence interval, �0.36 to �0.004) points/day (P = 0.05) and had reduced frequency by �0.21 (95% confidence interval, �0.37 to �0.05) points/day (P =0 .01). The PDM group had reduced sedation frequency by �0.18 (95% confidence interval, �0.36 to �0.004) points/day versus the NCH group (P = 0.04). By the fifth study day, the PDM patients received two fewer sedative doses (reduction of 38%) and had a reduction of 36% in sedation intensity. Conclusions Among ICU patients receiving acute ventilatory support for respiratory failure, PDM resulted in greater reduction in anxiety compared with usual care, but not compared with NCH. Concurrently, PDM resulted in greater reduction in sedation frequency compared with usual care or NCH, and greater reduction in sedation intensity compared with usual care but not compared with NCH.

Contributors to fatigue in patients receiving mechanical ventilatory support: A descriptive correlational study

To describe levels of fatigue and explore clinical factors that might contribute to fatigue in critically ill patients receiving mechanical ventilation. Descriptive, correlational design. Sample was a sub-set of patients enrolled in a randomised clinical trial testing patient-directed music for anxiety self-management. Clinical factors included age, gender, length of ICU stay, length of ventilatory support, illness severity (APACHE III), and sedative exposure (sedation intensity and frequency). Descriptive statistics and mixed models were used to address the study objectives. Medical and surgical intensive care units in the Midwestern United States. Fatigue was measured daily via a 100-mm Visual Analogue Scale, up to 25 days. A sample of 80 patients (50% female) receiving ventilatory support for a median 7.9 days (range 1-46) with a mean age of 61.2 years (SD 14.8) provided daily fatigue ratings. ICU admission APACHE III was 61.5 (SD 19.8). Baseline mean fatigue ratings were 60.7 (SD 27.9), with fluctuations over time indicating a general trend upward. Mixed models analysis implicated illness severity (β(se(β))=.27(.12)) and sedation frequency (β(se(β))=1.2(.52)) as significant contributors to fatigue ratings. Illness severity and more frequent sedative administration were related to higher fatigue ratings in these mechanically ventilated patients.

Patient-directed music therapy reduces anxiety and sedation exposure in mechanically-ventilated patients: A research critique

This research appraisal, guided by the CASP Randomised Controlled Trial Checklist, critiques a randomised, controlled trial of patient-directed music therapy compared to either noise-cancelling headphones or usual care. This study recruited 373 alert, mechanically-ventilated patients across five intensive care units in the United States. The Music Assessment Tool, administered by a music therapist, facilitated music selection by participants in the intervention group. Anxiety was measured using the VAS-A scale. Sedation exposure was measured by both sedation frequency and by sedation intensity using a daily sedation intensity score. Context for the data was supported by an environmental scan form recording unit activity and by written comments from nurses about the patient's responses to the protocol. Patient-directed music therapy allowed a significant reduction in sedation frequency compared to noise-cancelling headphones and usual care participants. Patient-directed music therapy led to significantly lower anxiety and sedation intensity compared to usual care, but not compared to noise-cancelling headphones.This is a robust study with clear aims and a detailed description of research methods and follow-up. While no participants were lost to follow-up, not all were included in the analysis: 37% did not have the minimum of two anxiety assessments for comparison and 23% were not included in sedation analysis. While some participants utilised the intervention or active control for many hours-per-day, half the music therapy participants listened for 12min or less per day and half of the noise-cancelling headphone participants did not appear to use them. While the results suggest that patient-directed music therapy and noise-cancelling headphones may be useful and cost-effective interventions that lead to an overall improvement in anxiety and sedation exposure, these may appeal to a subset of ICU patients. The self-directed use of music therapy and noise-cancelling headphones means these findings may not transfer to sedated or cognitively-impaired patients.

Diazepam or midazolam for orotracheal intubation in the ICU?

to compare clinical and cost effectiveness of midazolam and diazepam for urgent intubation. patients admitted to the Central ICU of the Santa Casa Hospital Complex in Porto Alegre, over the age of 18 years, undergoing urgent intubation during 6 months were eligible. Patients were randomized in a single-blinded manner to either intravenous diazepam or midazolam. Diazepam was given as a 5 mg intravenous bolus followed by aliquots of 5 mg each minute. Midazolam was given as an intravenous bolus of 5 mg with further aliquots of 2.5 mg each minute. Ramsay sedation scale 5-6 was considered adequate sedation. We recorded time and required doses to reach adequate sedation and duration of sedation. thirty four patients were randomized, but one patient in the diazepam group was excluded because data were lost. Both groups were similar in terms of illness severity and demographics. Time for adequate sedation was shorter (132 ± 87 sec vs. 224 ± 117 sec, p = 0.016) but duration of sedation was similar (86 ± 67 min vs. 88 ± 50 min, p = 0.936) for diazepam in comparison to midazolam. Total drug dose to reach adequate sedation after either drugs was similar (10.0 [10.0-12.5] mg vs. 15.0 [10.0-17.5] mg, p = 0.248). Arterial pressure and sedation intensity reduced similarly overtime with both drugs. Cost of sedation was lower for diazepam than for midazolam (1.4[1.4-1.8] vs. 13.9[9.4-16.2] reais, p <0.001). intubation using intravenous diazepam and midazolam is effective and well tolerated. Sedation with diazepam is associated to a quicker sedation time and to lower costs.

Smoking and weight among patients using clozapine

Background: Both obesity and smoking are common in schizophrenia patients taking clozapine, causing cardiovascular disease and premature deaths. Methods: Two hundred and thirty-seven patients with schizophrenia or related psychoses treated with clozapine completed the Liverpool University Neuroleptic Assessment Scale (LUNSERS) and a questionnaire including current height, weight, changes therein and smoking status. Aims: The aim of this study was to analyze weight and weight change in smoking and non-smoking patients taking clozapine. A possible interaction between obesity and smoking was explored. Results: No association was found between weight change and smoking status during clozapine treatment. There was no significant difference in body mass index (BMI) between non-smokers and smokers. In the analysis of covariance (ANCOVA) with BMI as the dependent variable, the best fitting model comprised age, sex, intensity of sedation, and reported amount of smoking as explanatory variables (ηp2= 0.116; P = 0.029; power = 0.750). None of the explanatory proportions of any single factor was significant. Conclusions: Estimated according to reported weight gain and BMI, no difference was found between smoking and non-smoking clozapine-treated patients. Number of cigarettes smoked explained BMI if age and sex were taken into account. This result is in line with the findings of some general population studies, where heavy smoking has been associated with a greater risk of obesity.

Randomized clinical trial of the effects of a combination of acepromazine with morphine and midazolam on sedation, cardiovascular variables and the propofol dose requirements for induction of anesthesia in dogs

The present study evaluated the effects of acepromazine combined with midazolam and morphine on sedation and cardiovascular variables as well as the propofol dose required for induction of anesthesia in dogs compared with acepromazine–morphine or midazolam–morphine. Dogs were randomly assigned to receive an intramuscular administration of (1) acepromazine (0.05mg/kg) with 0.5mg/kg of morphine (group AM, n=10), (2) midazolam (0.5mg/kg) with 0.5mg/kg of morphine (group MM, n=9), or (3) acepromazine with midazolam and morphine at the same doses (group AMM, n=10). After 30min, sedation was assessed by a numeric descriptive scale (NDS, range 0–3) and a simple numerical scale (SNS, range 0–10). Dogs were then administered IV propofol to allow endotracheal intubation.NDS and SNS scores were significantly higher in the AMM than in the MM group (P<0.05). There was a trend towards more dogs presenting with intense sedation (NDS=3) in AMM (6/10 dogs) compared with AM (1/10 dogs) and MM (1/9 dogs) (P=0.057). The propofol dose required for induction of anesthesia was significantly lower in AMM (4.0mg/kg) compared with MM (6.0mg/kg, P<0.01) but not AM (4.6mg/kg). Heart rate decreased in AM after treatment and after intubation. Blood pressure decreased in groups AM and AMM following treatment and in all groups after intubation. The combination AMM resulted in intense sedation more frequently than AM and MM, and provided the greatest sparing effect in the propofol dose. Administration of AM and AMM but not MM decreased blood pressure although hypotension was not recorded in healthy dogs.