Effect of Midazolam in Addition to Propofol and Opiate Sedation on the Quality of Recovery After Colonoscopy: A Randomized Clinical Trial.

BACKGROUND: There is a concern that midazolam, when used as a component of sedation for colonoscopy, may impair cognition and prolong recovery. We aimed to identify whether midazolam produced short- and longer-term effects on multiple dimensions of recovery including cognition. METHODS: A 2-center double-blinded, placebo-controlled, parallel-group, randomized, phase IV study with a 1:1 allocation ratio was conducted in adults ≥18 years of age undergoing elective outpatient colonoscopy, with sufficient English language proficiency to complete the Postoperative Quality of Recovery Scale (PostopQRS). Participants were administered either midazolam (0.04 mg·kg) or an equivalent volume of 0.9% saline before sedation with propofol with or without an opiate. The primary outcome was incidence of recovery in the cognitive domain of the PostopQRS on day 3 after colonoscopy, which was analyzed using a χ test. Secondary outcomes included recovery in other domains of the PostopQRS over time, time to eye-opening, and hospital stay, and patient and endoscopist satisfaction. All hypotheses were defined before recruitment. RESULTS: During September 2015 to June 2018, 406 patients were allocated to either midazolam (n = 201) or placebo (n = 205), with one withdrawn before allocation. There was no significant difference in recovery in the cognitive domain of the PostopQRS on day 3 after colonoscopy (midazolam 86.8% vs placebo 88.7%, odds ratio, 0.838; 95% confidence interval [CI], 0.42-1.683; P= .625). Furthermore, there was no difference in recovery over time in the cognitive domain of the PostopQRS (P = .534). Overall recovery of the PostopQRS increased over time but was not different between groups. Furthermore, there were no differences between groups for nociceptive, emotive, activities-of-daily-living domains of the PostopQRS. Patient and endoscopist satisfaction were high and not different. There were no differences in time to eye-opening (midazolam 9.4 ± 12.8 minutes vs placebo 7.3 ± 0.7 minutes; P = .055), or time to hospital discharge (midazolam 103.4 ± 1.4 minutes vs placebo 98.4 ± 37.0 minutes; P = .516). CONCLUSIONS: The addition of midazolam 0.04 mg·kg as adjunct to propofol and opiate sedation for elective colonoscopy did not show evidence of any significant differences in recovery in the cognitive domain of the PostopQRS, overall quality of recovery as measured by the PostopQRS, or emergence and hospital discharge times. The use of midazolam should be determined by the anesthesiologist.

A randomized trial of desflurane or sevoflurane on postoperative quality of recovery after knee arthroscopy.

BACKGROUND: Studies have described different recovery profiles of sevoflurane and desflurane typically early after surgery. METHODS: We conducted a randomized superiority trial to determine whether Overall Recovery 3 days after knee arthroscopy would be superior with desflurane. Adult participants undergoing knee arthroscopic surgery with general anesthesia were randomized to either desflurane or sevoflurane general anesthesia. Intraoperative and postoperative drugs and analgesics were administered at the discretion of the anesthesiologist. Postoperative quality of recovery was assessed using the "Postoperative Quality of Recovery Scale". The primary outcome was Overall Recovery 3 days after surgery and secondary outcomes were individual recovery domains at 15 minutes, 40 minutes, 1 day, 3 days, 1 month, and 3 months. Patients and researchers were blinded. RESULTS: 300 patients were randomized to sevoflurane or desflurane (age 51.7±14.1 vs. 47.3±13.5 years; duration of anesthesia 24.9±11.1 vs. 23.3±8.3 minutes). The proportion achieving baseline or better scores in all domains increased over the follow-up period in both groups but was not different at day 3 (sevoflurane 43% vs. desflurane 37%, p = 0.314). Similarly, rates of recovery increased over time in the five subdomains, with no differences between groups for physiological, p = 0.222; nociceptive, p = 0.391; emotive, p = 0.30; Activities-of-daily-living, p = 0.593; and cognitive recovery, p = 0.877. CONCLUSION: No significant difference in the quality of recovery scale could be shown using sevoflurane or desflurane general anesthesia after knee arthroscopy in adult participants.

A human volunteer study to identify variability in performance in the cognitive domain of the postoperative quality of recovery scale.

BACKGROUND: The Postoperative Quality of Recovery Scale found lower than anticipated recovery in the cognitive domain. The definition of cognitive recovery did not allow for performance variability, and may have been too sensitive. This study aimed to examine variability in cognitive performance in volunteers. METHODS: One hundred forty-three volunteers completed the cognitive domain questions at baseline, after 15 min and 40 min, and on days 1 and 3. Delivery via face-to-face interview was conducted for the first three measurements, and then randomized for day 1 and 3 measurements (face-to-face only, telephone only, telephone then face-to-face, face-to-face then telephone). RESULTS: All volunteers answered orientation correctly. Mean change scores for other tests were positive, indicating a modest learning effect. There were no significant differences between methods of delivery (all P > 0.05). Due to variability in volunteers' performances, the authors propose a new scoring system to introduce a tolerance factor in scoring cognitive recovery. The proposed revised change from baseline scores are: orientation 0 or higher, digits forward -2 or higher, digits back -1 or higher, word recall -3 or higher, and word generation -3 or higher. This resulted in approximately 95% volunteers classed as "recovered" for each test item, and recovery for the domains ranged from 82.6 to 89.1%. The initial feasibility study was reanalyzed and cognitive recovery increased at all assessment times. At 3 days, cognitive recovery was found to increase from 33.5 to 86.4%. CONCLUSION: The authors recommend adoption of the new method for scoring cognitive recovery in the Postoperative Quality of Recovery Scale. Telephone or face-to-face delivery was equivalent and either method can be reliably applied.

Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions.

BACKGROUND: Asthma is a chronic inflammatory disease with increasing incidence worldwide. Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 that prevents the breakdown of cyclic adenosine monophosphate levels, leading to inhibition of proinflammatory signaling. OBJECTIVE: The objective of this study was to investigate the effects of repeated doses of 250 or 500 microg of roflumilast on asthmatic airway responses to allergen. METHODS: Twenty-three patients with mild asthma with an FEV1 of 70% of predicted value or greater were enrolled in a randomized, double-blind, placebo-controlled, 3-period crossover study. Patients participated in 3 treatment periods (7-10 days) separated by washout periods (2-5 weeks). Patients received 250 microg of oral roflumilast, 500 microg of roflumilast, or placebo once daily. Allergen challenge was performed at the end of each treatment period, followed by FEV1 measurements over the ensuing 24 hours. RESULTS: Late asthmatic reactions (LARs) were reduced by 27% (P = .0110) and 43% (P = .0009) in patients treated with 250 and 500 microg of roflumilast, respectively, versus placebo. Roflumilast, 250 and 500 microg, also attenuated early asthmatic reactions by 25% (P = .0038) and 28% (P = .0046), although not to the same extent as LAR attenuation. Roflumilast was well tolerated. No serious adverse events or discontinuations caused by adverse events were reported. CONCLUSION: Once-daily oral roflumilast modestly attenuated early asthmatic reactions and, to a greater extent, LARs to allergen in patients with mild allergic asthma. Pronounced suppression of late responses in an allergen challenge model suggests that roflumilast might have anti-inflammatory activity, which could provide clinical efficacy in chronic inflammatory pulmonary diseases, such as asthma.

Rhinovirus is associated with severe asthma exacerbations and raised nasal interleukin-12.

BACKGROUND: Rhinovirus (RV) is associated with asthma exacerbations in longitudinal studies, but the role in patients with acute severe asthma who require admission to a hospital emergency room remains to be fully defined. The cytokines interleukin-10 (IL-10) and IL-12 may be elevated or suppressed by viral infections and contribute to a worsening of airway inflammation in asthmatics. OBJECTIVES: We assessed the association of RV with acute severe asthma and nasal IL-10 and IL-12. METHODS: Patients admitted to a hospital emergency asthma service had nasal aspirates (NAs) taken and peak expiratory flow (PEF) measured on admission and again 7, 28 and 56 days after admission. RV was sought in all NAs using a validated polymerase chain reaction assay and IL-10 and IL-12 were measured on admission and after 56 days in a subgroup of 22 asthmatics and 6 normal controls. RESULTS: Thirty-seven asthmatics with a reduced PEF (% predicted) of 50.4 +/- 2.5% (mean +/- SEM) on admission were studied. RV was detected in NAs of 13 patients (35%) on admission, in 6 of the 13 patients after 7 days (16%), in 1 patient after 28 and 56 days and was absent in controls. IL-10 was not increased on admission or after 56 days. Measurements of IL-12 were raised on admission compared to 56 days later in asthmatics with RV detectable (p = 0.04). In asthmatics without RV, nasal IL-12 levels were correlated with PEF measurements over this period (r = 0.5, p < 0.05). CONCLUSIONS: A temporal relationship between the presence of nasal RV and emergency room admission for acute severe asthma was found in one third of patients. Low levels of IL-10 during RV infections could contribute to unopposed synthesis of pro-inflammatory cytokines whilst increases in IL-12 may amplify nasal and endobronchial inflammation.

Risk factors for near-fatal asthma--a case-control study in a Western Cape teaching hospital.

BACKGROUND AND OBJECTIVES: To evaluate risk factors for asthma death such as access to health care, over-use of beta 2-agonists or under-use of inhaled corticosteroids in the Western Cape (WC) population, using near-fatal asthma (NFA) as a surrogate marker. SUBJECTS AND METHODS: Patients with NFA (cases) admitted to a WC teaching hospital were compared with patients with acute asthma in a case-control study using a structured questionnaire, clinical examination, arterial blood gas measurements, chest radiograph and pulmonary function measurements. RESULTS: Sixteen patients with NFA (cases) and 55 with acute asthma (controls) were prospectively enrolled. Duration of asthma, gender, smoking status and ethnicity were similar. Cases had significantly more previous mechanical ventilation (P < 0.05) and a trend towards more previous intensive care unit (ICU) admissions. No significant differences were found in primary health care variables. CONCLUSION: Our study demonstrates that patients with NFA constitute a significant number of emergency room (ER) admissions for acute asthma (30%) in our population. Similar to other studies, there was a trend for NFA toward more previous ICU admissions and mechanical ventilation. Relative under-use of beta 2-agonists the day before admission and fewer ER visits during the previous year in the NFA group, suggests an impaired perception of the severity of disease or a more rapid onset of symptoms. Negative factors such as inability to access health care or lack of medication supply were similar in both groups. The challenge remains to identify and manage high-risk patients effectively.