Low-dose ketamine does not improve the speed of recovery from depression in electroconvulsive therapy: a randomized controlled trial

Objective: Electroconvulsive therapy (ECT) is a well-established therapeutic intervention for major depressive disorder. Recent literature has shown that the anesthetic agent ketamine has some antidepressant properties at low doses and may be an alternative therapy for treatment-resistant major depressive disorder. We hypothesized that the use of low-dose ketamine as an anesthetic adjunct in ECT would more rapidly improve depression while maintaining hemodynamic stability than ECT with propofol alone. Methods: Institutional ethics approval was obtained, and the use of ketamine in this study was approved by Health Canada. This is a randomized, double-blinded, placebo-controlled trial that involved ketamine administration at 0.5 mg/kg IV in addition to propofol anesthesia for ECT. The primary outcome was the number of ECT treatments required to achieve a 50% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included the number of ECT treatments required to achieve a 25% reduction in MADRS score, as well as any differences in the Clinical Global Impression Scale for Severity, hemodynamic variables, and seizure duration. Adverse events were recorded for safety assessment. Results: A total of 45 patients completed the study. No difference was found between groups with respect to the primary or secondary outcomes. The ketamine group showed a trend towards a decreased dose of propofol required to achieve adequate anesthesia. No adverse events were reported. Conclusion: Low-dose ketamine does not improve psychiatric outcomes in the setting of propofol-based anesthesia for ECT. Specifically, ketamine did not reduce the number of ECT sessions necessary to achieve a 50 or 25% reduction in MADRS scores. Reassuringly, the fact that no differences in hemodynamic variables or unexpected adverse events occurred suggests that low-dose ketamine may be safely used in this setting should clinical indications warrant its use. Clinical trial registration: ClinicalTrials.gov, NCT02579642

Low-dose ketamine does not improve the speed of recovery from depression in electroconvulsive therapy: a randomized controlled trial.

OBJECTIVE: Electroconvulsive therapy (ECT) is a well-established therapeutic intervention for major depressive disorder. Recent literature has shown that the anesthetic agent ketamine has some antidepressant properties at low doses and may be an alternative therapy for treatment-resistant major depressive disorder. We hypothesized that the use of low-dose ketamine as an anesthetic adjunct in ECT would more rapidly improve depression while maintaining hemodynamic stability than ECT with propofol alone. METHODS: Institutional ethics approval was obtained, and the use of ketamine in this study was approved by Health Canada. This is a randomized, double-blinded, placebo-controlled trial that involved ketamine administration at 0.5 mg/kg IV in addition to propofol anesthesia for ECT. The primary outcome was the number of ECT treatments required to achieve a 50% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included the number of ECT treatments required to achieve a 25% reduction in MADRS score, as well as any differences in the Clinical Global Impression Scale for Severity, hemodynamic variables, and seizure duration. Adverse events were recorded for safety assessment. RESULTS: A total of 45 patients completed the study. No difference was found between groups with respect to the primary or secondary outcomes. The ketamine group showed a trend towards a decreased dose of propofol required to achieve adequate anesthesia. No adverse events were reported. CONCLUSION: Low-dose ketamine does not improve psychiatric outcomes in the setting of propofol-based anesthesia for ECT. Specifically, ketamine did not reduce the number of ECT sessions necessary to achieve a 50 or 25% reduction in MADRS scores. Reassuringly, the fact that no differences in hemodynamic variables or unexpected adverse events occurred suggests that low-dose ketamine may be safely used in this setting should clinical indications warrant its use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579642.

Pain management during labor and vaginal birth.

Neuraxial analgesia provides excellent pain relief in labor. Optimizing initiation and maintenance of neuraxial labor analgesia requires different strategies. Combined spinal-epidurals or dural puncture epidurals may offer advantages over traditional epidurals. Ultrasound is useful in certain patients. Maintenance of analgesia is best achieved with a background regimen (either programmed intermittent boluses or a continuous epidural infusion) supplemented with patient-controlled epidural analgesia and using dilute local anesthetics combined with opioids such as fentanyl. Nitrous oxide and systemic opioids are also used for pain relief. Nitrous oxide may improve satisfaction despite variable effects on pain. Systemic opioids can be administered by healthcare providers or using patient-controlled analgesia. Appropriate choice of drug should take into account the stage and progression of labor, local safety protocols, and maternal and fetal/neonatal side effects. Pain in labor is complex, and women should fully participate in the decision-making process before any one modality is selected.

Evaluation of Opioid Use With Split Doses of Oral Opioids in a Postcesarean Delivery Analgesia Order Set.

OBJECTIVE: To evaluate whether an order set change that halved the initial dose of oxycodone and allowed the remainder to be given 1 hour later, if requested, was associated with reduced opioid use and side effects after cesarean delivery. METHODS: This retrospective, clinical practice study reviewed electronic medical records after implementation of a new order set for cesarean delivery. Oxycodone orders changed from 5 mg (for verbal pain score of 4/10 or lower) and 10 mg (for 5-10/10) to 2.5 mg (for verbal pain score 1-4/10) or 5 mg (for 5-10/10), and the patient requesting pain relief, with a nurse check within 1 hour to administer another 2.5 or 5 mg, respectively, if needed. The primary outcome was opioid use (in intravenous morphine equivalents) in the first 48 hours. Secondary outcomes included incidence and treatment of nausea or vomiting and pruritis, average and peak verbal pain scores within 48 hours, and satisfaction. RESULTS: The records of 1,050 women were examined (542 before and 508 after the change). Opioid use in the first 48 hours was lower after the practice change (median [interquartile range] 10.0 [1.3-25.0] mg before vs 4.4 [0-12.5] mg after; P<.001). A small increase in average verbal pain score occurred (mean [SD] 1.8 [1.0] before vs 2.0 [1.3] after; difference -0.2; 95% CI -0.3 to -0.04). Peak verbal pain score (5.9 [2.0] before vs 6.0 [2.1] after; difference -0.1; 95% CI -0.4 to 0.1) and mean (SD) satisfaction score (97.7 [7.2] before vs 97.1 [7.5] after; difference 0.6, 95% CI -0.5 to 1.6) did not change. Fewer patients reported postoperative nausea or vomiting (30.9% before vs 19.3% after; odds ratio 0.5; 95% CI 0.4 to 0.7). CONCLUSION: Split doses of oxycodone were associated with 56% reduction in 48 hours opioid use after cesarean delivery.

Transesophageal Echocardiographic Observation of Caval Thrombus Followed by Intraoperative Placement of Inferior Vena Cava Filter for Presumed Pulmonary Embolism During Cesarean Hysterectomy for Placenta Percreta: A Case Report.

During a cesarean hysterectomy for placenta percreta, transesophageal echocardiography was used to monitor volume status and guide resuscitation. After delivery of the neonate but before massive surgical hemorrhage, a thrombus appeared in the inferior vena cava. Roughly 3 hours later, the patient had hemodynamic changes consistent with an intraoperative pulmonary embolism. Boluses of epinephrine stabilized the patient. An inferior vena cava filter was placed via an in situ internal jugular central venous cannula to prevent further embolic events. We believe transesophageal echocardiography is a useful monitor during surgery for placenta percreta.

Time to consultation and disease-modifying antirheumatic drug treatment of patients with rheumatoid arthritis--northern Alberta perspective.

OBJECTIVE: To determine the timeliness of consultation and initiation of disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) referred to rheumatologists. METHODS: The first part of the study was a review of the charts of 151 patients with RA followed by 3 rheumatologists. The outcome measure was the interval between symptom onset and consultation with a rheumatologist. The second part of the study involved a chart review of 4 family physician practices in a small urban center in order to determine the accuracy of diagnostic coding (International Classification of Diseases; ICD-9) of RA, as well as the proportion of patients with RA seen by a rheumatologist. Finally, a survey was sent to primary care physicians at a group of walk-in clinics to determine what percentage of their patients with RA were referred to a rheumatologist and, concerning referral patterns, how likely it is they would refer a confirmed or suspected RA patient to a rheumatologist. RESULTS: Patients with RA referred to rheumatologists in this sample were seen by a rheumatologist at a mean of 9.8 months (median 5 mo, range 0-129 mo) after symptom onset, and mean 1.2 months (median 4.0 mo, range 0-8 mo) after being referred by their primary care physician. All referred patients with confirmed RA were started on DMARD within 1 week of initial consultation. Primary care physicians would refer suspected RA patients 99.5% of the time (median 100, range 90-100%), and 87.6% (median 90, range 50-100%) of patients with confirmed RA would have seen a rheumatologist at least once. A chart review showed that, in a select group of family physicians, 70.9% (22/31) of patients coded as RA per the ICD-9 did indeed have RA and all had seen a rheumatologist for their condition. CONCLUSION: In Northern Alberta, patients with RA are seen and started on DMARD therapy in a timely fashion. Most of the delay is at the primary care level, suggesting a need for improved education of patients and primary care physicians rather than a formal triage system.

Intraocular lens capture in combined cataract extraction and pars plana vitrectomy: comparison of 1-piece and 3-piece acrylic intraocular lenses.

PURPOSE: To report and compare the incidence of pupillary capture and posterior synechiae formation after combined cataract extraction and pars plana vitrectomy (PPV) with a 1-piece versus a 3-piece acrylic intraocular lens (IOL). SETTING: Royal Alexandra Hospital Eye Clinic, University of Alberta, Edmonton, Alberta, Canada. DESIGN: Comparative case series. METHODS: Consecutive patients who had combined cataract extraction with PPV were retrospectively reviewed. The outcomes in patients who received a 1-piece acrylic IOL and those who received a 3-piece acrylic IOL were compared. The proportion of patients with pupillary IOL capture and/or posterior synechiae postoperatively was recorded. RESULTS: The cohort comprised 145 patients. All cases of IOL capture occurred in eyes with a 1-piece IOL (n = 7; 7.7%); the difference between the 1-piece IOL group and the 3-piece IOL group was statistically significant (P = .043). There was no significant difference between the 2 IOL types in the rate of posterior synechiae formation. Regression analysis showed that the odds of posterior synechiae formation were significantly higher in cases in which perfluoropropane (C(3)F(8)) (odds ratio [OR], 24.01; P = .006), sulfur hexafluoride (SF(6)) (OR, 25.23; P = .007), or silicone oil (OR, 47.78; P<.001) was used. CONCLUSIONS: The incidence of IOL capture was significantly greater after implantation of a 1-piece IOL than after implantation of a 3-piece IOL during combined cataract extraction and PPV. Posterior synechiae formation was associated with the use of silicone oil, SF(6), or C(3)F(8).

The subcellular distribution of calnexin is mediated by PACS-2.

Calnexin is an endoplasmic reticulum (ER) lectin that mediates protein folding on the rough ER. Calnexin also interacts with ER calcium pumps that localize to the mitochondria-associated membrane (MAM). Depending on ER homeostasis, varying amounts of calnexin target to the plasma membrane. However, no regulated sorting mechanism is so far known for calnexin. Our results now describe how the interaction of calnexin with the cytosolic sorting protein PACS-2 distributes calnexin between the rough ER, the MAM, and the plasma membrane. Under control conditions, more than 80% of calnexin localizes to the ER, with the majority on the MAM. PACS-2 knockdown disrupts the calnexin distribution within the ER and increases its levels on the cell surface. Phosphorylation by protein kinase CK2 of two calnexin cytosolic serines (Ser554/564) reduces calnexin binding to PACS-2. Consistent with this, a Ser554/564 Asp phosphomimic mutation partially reproduces PACS-2 knockdown by increasing the calnexin signal on the cell surface and reducing it on the MAM. PACS-2 knockdown does not reduce retention of other ER markers. Therefore, our results suggest that the phosphorylation state of the calnexin cytosolic domain and its interaction with PACS-2 sort this chaperone between domains of the ER and the plasma membrane.