Matthew J. Ritter

Serial infusions of low-dose ketamine for major depression

Background: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients. Side effects during the infusions have been common. It is not known whether serial infusions or lower infusion rates result in greater efficacy. Methods: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0.5 mg/kg administered over 100 min until either remission was achieved or four infusions were given. Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions. Results: Five of 10 patients achieved remission status. There were no significant increases on the BPRS or YMRS. Two of the remitting patients sustained their improvement throughout the four week follow-up period. Conclusions: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care. Serial ketamine infusions appear to be more effective than a single infusion. Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.

Ondansetron-Induced Multifocal Encephalopathy

We treated a patient who developed transient multifocal encephalopathy with extrapyramidal symptoms (oromandibular dystonia, oculogyric crisis, and limb dystonia) in temporal proximity to ondansetron administration on emergence from general anesthesia. No other medications known to cause extrapyramidal reactions were administered. Although these symptoms resolved fully, the presentation was dramatic and resembled the symptoms of structural brain injury. Ondansetron is used frequently as an antiemetic agent in many clinical settings and is not limited to surgical patients. Therefore, the entire medical community should be cognizant of this potential adverse reaction.

Continuation phase intravenous ketamine in adults with treatment-resistant depression.

BACKGROUND Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression. METHODS Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24h following each infusion, at the last acute-phase observation, and during continuation and post-continuation follow-up (acute phase remitters only). RESULTS Of the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment; however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up. LIMITATIONS This was an uncontrolled feasibility study with a small sample size. CONCLUSIONS The continuation-phase administration of ketamine at weekly intervals to patients with treatment-resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine. CLINICALTRIALS. GOV IDENTIFIER NCT02094898.

Outcomes of cardiopulmonary resuscitation and predictors of survival in patients undergoing coronary angiography including percutaneous coronary interventions.

We studied the outcome of cardiopulmonary resuscitation (CPR) in patients undergoing coronary angiography (CA) and/or percutaneous coronary interventions (PCI). Of 51,985 CA and PCI patients treated between January 1, 1990, and December 31, 2000, 114 required CPR. Records were reviewed for relationships between patient characteristics and various procedures and short-term survival. Long-term survival was compared with that of a matched cohort of patients who did not have an arrest during catheterization and a matched cohort from the general Minnesota population. Over the 11-year period, the overall incidence of CPR was 21.9 per 10,000 procedures. This rate decreased from 33.9 per 10,000 before 1995 to 13.1 per 10,000 after 1995. Overall survival to hospital discharge after CPR was 56.1%. Survival to discharge was less frequent with a history of congestive heart failure, previous coronary artery bypass graft surgery, hemodynamic instability during the procedure, and with prolonged or emergent catheterizations. Pulseless electrical activity (versus asystole or ventricular fibrillation) indicated very poor short-term survival. Interestingly, short-term survival was not related to the extent of coronary artery disease. Long-term survival of patients who survived cardiac arrest was comparable to that of those who did not have arrest during catheterization. In conclusion, the incidence of periprocedural CPR during diagnostic or interventional coronary procedures decreased after 1995. Patients who received CPR in the cardiac catheterization lab have a remarkably frequent survival to hospital discharge rate. Long-term survival of these patients is only minimally reduced.

Some considerations of the tolerability of ketamine for ECT anesthesia: a case series and review of the literature.

Most anesthetic agents used for electroconvulsive therapy (ECT) have few intrinsic adverse effects. Ketamine, however, is well known to be associated with a variety of adverse effects including nausea, dizziness, and psychotomimetic phenomena. Over the past several decades, there have been numerous reports on the use of ketamine for ECT anesthesia, with varied assessments on how prominent these adverse effects are in the ECT situation. Ketamine has received a resurgence of interest as an ECT anesthetic of late owing to its established independent antidepressant effects and to theoretical reasons why it might lessen the cognitive adverse effects of ECT. In this case series, the author reviews the experience with 14 patients who had undergone ECT who were switched to ketamine as anesthetic from methohexital at the preference of the treating anesthesiologist. All 14 patients spontaneously reported a strong preference not to be given ketamine again due to bothersome adverse effects. The latter consisted of either vestibular-type symptoms (nausea/vomiting, dizziness, and vertigo) or psychotomimetic effects (dissociative phenomena). It is concluded that ketamine is not free of adverse effects when used as an ECT anesthetic. Electroconvulsive therapy clinicians should be vigilant about assessing for these effects when ketamine is used, and consideration should be given to using a benzodiazepine such as diazepam or midazolam at seizure termination when ketamine anesthesia is used to prevent bothersome adverse effects seen upon awakening.

Standardized practice design with electronic support mechanisms for surgical process improvement: reducing mechanical ventilation time.

Background:Hospital surgical care is complex and subject to unwarranted variation. Objective:As part of a multiyear effort, we sought to reduce variability in intraoperative care and management of mechanical ventilation in cardiac surgery. We identified a patient population whose care could be standardized and implemented a protocol-based practice model reinforced by electronic mechanisms. Methods:In a large cardiac surgery practice, we built a standardized practice model between 2009 and 2011. We compared mechanical ventilation time before (2008) and after (2012) implementation. To ensure groups were comparable, propensity analysis matched patients from the 2 operative years. Results:In 2012, more than 50% of all cardiac surgical patients were managed with our standardized care model; of those, 769 were one-to-one matched with patients undergoing surgery in 2008. Patients had a mix of coronary artery bypass grafting, valve surgery, and combined procedures. Our practice model reduced median mechanical ventilation duration from 9.3 to 6.3 hours (2008 and 2012) (P < 0.001) and intensive care unit length of stay from 26.3 to 22.5 hours (P < 0.001). Reintubation and intensive care unit readmission were unchanged. Variability in ventilation time was also reduced. Conclusions:We demonstrate that in more than 50% of all cardiac surgical patients, a standardized practice model can be used to achieve better results. Clinical outcomes are improved and unwarranted variability is reduced. Success is driven by clear patient identification and well-defined protocols that are clearly communicated both by electronic tools and by empowerment of bedside providers to advance care when clinical criteria are met.

Anesthetic-induced pain on injection in electroconvulsive therapy: review of the literature and suggestions for prevention.

Pain on injection (angialgia) is a common adverse effect of anesthetic medications, especially propofol and methohexital, which are both used for electroconvulsive therapy (ECT). In this review, the authors survey some general literature on angialgia incidence, mechanisms, and prevention efforts in non-ECT settings and follow this with a review of similar topics relevant to ECT. They review practical methods of angialgia prevention for ECT patients. The methods with the best research basis include the use of an antecubital vein for intravenous access as well as the local anesthetic lidocaine. Regarding the latter, concerns regarding shortening of seizure duration during ECT have been raised. If lidocaine is used for angialgia in ECT, low doses should be administered to avoid possible interference with ictal electroencephalogram expression. Other methods worth studying further for angialgia during ECT include use of the antiemetic agent metoclopramide and high-potency opiates.

A “Fundamentals” Train-the-Trainer Approach to Building Pediatric Critical Care Expertise in the Developing World

Pediatric Fundamental Critical Care Support (PFCCS) is an educational tool for training non-intensivists, nurses, and critical care practitioners in diverse health-care settings to deal with the acute deterioration of pediatric patients. Our objective was to evaluate the PFCCS course as a tool for developing a uniform, reproducible, and sustainable model for educating local health-care workers in the optimal management of critically ill children in the Republic of Georgia. Over a period of 18 months and four visits to the country, we worked with Georgian pediatric critical care leadership to complete the following tasks: (1) survey health-care needs within the Republic of Georgia, (2) present representative PFCCS lectures and simulation scenarios to evaluate interest and obtain “buy-in” from key stakeholders throughout the Georgian educational infrastructure, and (3) identify PFCCS instructor candidates. Georgian PFCCS instructor training included the following steps: (1) US PFCCS consultant and content experts presented PFCCS course to Georgian instructor candidates. (2) Simulation learning principles were taught and basic equipment was acquired. (3) Instructor candidates presented PFCCS to Georgian learners, mentored by PFCCS course consultants. Objective evaluation and debriefing with instructor candidates concluded each visit. Between training visits Georgian instructors translated PFCCS slides to the Georgian language. Six candidates were identified and completed PFCCS instructor training. These Georgian instructors independently presented the PFCCS course to 15 Georgian medical students. Student test scores improved significantly from pretest results (n = 14) (pretest: 38.7 ± 7 vs. posttest 62.7 ± 6, p < 0.05). A Likert-type scale of 1 to 5 (1 = not useful or effective, 5 = extremely useful or effective) was used to evaluate each student’s perception regarding (1) relevance of course content to clinical work students rated as median (IQR): (a) relevance of PFCCS content to clinical work, 5 (4–5); (b) effectiveness of lecture delivery, 4 (3–4); and (c) value of skill stations for clinical practice, 5 (4–5). Additionally, the mean (±SD) responses were 4.6 (±0.5), 3.7 (±0.6), and 4.5 (±0.6), respectively. Training local PFCCS instructors within an international environment is an effective method for establishing a uniform, reproducible, and sustainable approach to educating health-care providers in the fundamentals of pediatric critical care. Future collaborations will evaluate the clinical impact of PFCCS throughout the Georgian health-care system.

Corrigendum to “Continuation phase intravenous ketamine in adults with treatment-resistant depression” [J. Affect. Disord. 206 (2016) 300–304]

We recently became aware of an error in the classification of one study subjects positive treatment response status at the end of the post-continuation phase of this study. We originally reported that all 5 subjects who achieved depressive symptom remission during the acute phase of the study (and thus received 4 weekly continuation phase ketamine infusions) were classified as responders at the end of the post-continuation phase. However, one of these 5 subjects was misclassified as a positive treatment responder at the end of the post-continuation phase. Therefore, only 4 of these 5 patients were positive treatment responders at the end of the post-continuation phase. Although our main conclusions are not changed, we believe that it is our responsibility to report the error and updated results. The authors would like to apologise for any inconvenience caused.