In this editorial, we emphasise the efficacy and challenges of using ketamine in treatment-resistant depression. We highlight the need for comprehensive evidence-based guidelines to manage the use of both licensed and off-licence ketamine formulations and discuss recent efforts by Beaglehole et al to develop ketamine guidelines in New Zealand. We finally advocate for national registries to monitor ketamine therapy, ensuring its responsible and effective use in the management of depression.

Ketamine is a phencyclidine (PCP) derivative, which primarily acts as a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Ketamine serves as an analgesic and a dissociative sedative that produces potent analgesia, sedation, and amnesia while preserving spontaneous respiratory drive. It is rapidly gaining acceptance in the management of pain as multiple studies have demonstrated its reliable efficacy and a wide margin of safety. This article reviews some of these studies, the history of ketamine, and its pharmacological and pharmacokinetic properties. The article also discusses the use of ketamine in the trauma setting, including joint reductions, procedures, sedation, and pain control, as well as dosing recommendations.

BACKGROUND: The evidence base for racemic ketamine treatment for treatment-resistant major depressive disorder (TRD) continues to expand, but there are major challenges translating this evidence base into routine clinical care.
OBJECTIVE: To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services.
METHODS: We consulted with senior leadership, clinical pharmacy, psychiatrists, nursing, service users and Māori mental health workers on issues relating to ketamine treatment. We prepared treatment guidelines taking the evidence base for ketamine treatment and the consultation into account.
RESULTS: Ketamine treatment guidance is reported. This offers two treatment pathways, including a test of ketamine responsiveness with intramuscular ketamine and the dominant use of oral ketamine for a 3-month course to maximise the opportunity for the short-term benefits of ketamine to accumulate.
CONCLUSIONS: We have responded to the challenges of translating the evidence base for ketamine treatment into a form suitable for routine care.

Background: Although opioids are used first line for cancer pain and commonly for complex noncancer pain, there are risks associated with their use and not effective for all types of pain. There\'s a need to identify and develop clinical practice guidelines for nonopioids for the treatment of refractory pain. Methods: Our study collected information from national clinical practice guidelines for ketamine, lidocaine, and dexmedetomidine with the aim to identify consensus among the different practices. Results: Fifteen institutions nationally participated in the study and only nine of those institutions had guidelines and were permitted by their health system to share them. Of the institutions that participated, 44% had guidelines for ketamine and lidocaine, and only two institutions (22%) had guidelines for ketamine, lidocaine, and dexmedetomidine for refractory pain. There were variations in restriction of the level of care and prescribers, dosing, and determination of efficacy. There were trends of consensus in monitoring for side effects. Conclusion: This study serves as a starting point for a snapshot of the use of ketamine, lidocaine, and dexmedetomidine for refractory pain, but further studies and increased participation of institutions are needed to develop consensus clinical practice guidelines.

Chest wall injury in older adults is a significant cause of morbidity and mortality. Optimal nonsurgical management strategies for these patients have not been fully defined regarding level of care, incentive spirometry (IS), noninvasive positive pressure ventilation (NIPPV), and the use of ketamine, epidural, and other locoregional approaches to analgesia.
Relevant questions regarding older patients with significant chest wall injury with patient population(s), intervention(s), comparison(s), and appropriate selected outcomes were chosen. These focused on intensive care unit (ICU) admission, IS, NIPPV, and analgesia including ketamine, epidural analgesia, and locoregional nerve blocks. A systematic literature search and review were conducted, our data were analyzed qualitatively and quantitatively, and the quality of evidence was assessed per the Grading of Recommendations Assessment, Development, and Evaluation methodology. No funding was used.
Our literature review (PROSPERO 2020-CRD42020201241, MEDLINE, EMBASE, Cochrane, Web of Science, January 15, 2020) resulted in 151 studies. Intensive care unit admission was qualitatively not superior for any defined cohort other than by clinical assessment. Poor IS performance was associated with prolonged hospital length of stay, pulmonary complications, and unplanned ICU admission. Noninvasive positive pressure ventilation was associated with 85% reduction in odds of pneumonia ( p < 0.0001) and 81% reduction in odds of mortality ( p = 0.03) in suitable patients without risk of airway loss. Ketamine use demonstrated no significant reduction in pain score but a trend toward reduced opioid use. Epidural and other locoregional analgesia techniques did not affect pneumonia, length of mechanical ventilation, hospital length of stay, or mortality.
We do not recommend for or against routine ICU admission. We recommend use of IS to inform ICU status and conditionally recommend use of NIPPV in patients without risk of airway loss. We offer no recommendation for or against ketamine, epidural, or other locoregional analgesia.
Systematic Review/Meta-analysis; Level IV.

BACKGROUND: Bipolar disorder is a mood dysregulation characterized by recurrent symptoms and episodes of mania, hypomania, depression, and mixed mood. The complexity of treating patients with bipolar disorder prompted the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) to publish the first Taiwan consensus on pharmacological treatment of bipolar disorders in 2012. This paper presents the updated consensus, with changes in diagnostic criteria (i.e., mixed features) and emerging pharmacological evidence published up to April 2022.
METHODS: Our working group systemically reviewed the clinical research evidence and international guidelines and determined the levels of evidence for each pharmacological treatment on the basis of the most recent World Federation of Societies of Biological Psychiatry grading system. Four clinical-specific issues were proposed. The current TSBPN Bipolar Taskforce then discussed research evidence and clinical experience related to each treatment option in terms of efficacy and acceptability and then appraised final recommendation grades through anonymous voting.
RESULTS: In the updated consensus, we include the pharmacological recommendations for bipolar disorder with mixed features considering its high prevalence, the severe clinical prognosis, and the absence of approved medications. Cariprazine, lurasidone, repetitive transcranial magnetic stimulation, and ketamine are incorporated as treatment options. In the maintenance phase, the application of long-acting injectable antipsychotics is emphasized, and the hazards of using antidepressants and conventional antipsychotics are proposed.
CONCLUSIONS: This updated Taiwan consensus on pharmacological treatment for bipolar disorder provides concise evidence-based and empirical recommendations for clinical psychiatric practice. It may facilitate treatment outcome improvement in patients with bipolar disorder.

The American Academy of Orthopaedic Surgeons Clinical Practice Guideline \"Pharmacologic, Physical, and Cognitive Pain Alleviation for Musculoskeletal Extremity/Pelvis Surgery\" is a summary of the available literature designed to help guide surgeons provide a safe and effective means of pain alleviation for orthopaedic surgery patients. The following case study demonstrates these guidelines at work in a patient undergoing total shoulder arthroplasty. The recommendations listed in the following sentences are from the Clinical Practice Guideline. Preoperative patient education regarding the effects of opioids and benefits of early termination may help patients discontinue opioids earlier in their postoperative course. Perioperative use of intravenous ketamine and regional anesthesia continuous peripheral nerve catheters help reduce pain scores and decrease opioid use. Postoperative cryotherapy may provide a modest benefit in reducing pain scores. Postoperative cyclooxygenase-2 selective nonsteroidal anti-inflammatory medications (NSAIDs) and oral acetaminophen improve pain and decrease opioid use. Combination opioid/NSAIDs may provide a modest improvement in pain scores at the expense of NSAID dose optimization in the postoperative period. Gabapentin has not been shown to improve patient outcomes; however, pregabalin may decrease pain and opioid use after total joint arthroplasty.

暂无摘要。

Battlefield pain occurs in combat casualties who experience multiple severe injuries. The nature of battlefield scenarios requires a distinct approach to battlefield pain research. A battlefield pain summit was thus convened to identify shortcomings in the current understanding of battlefield pain management, review the current state of battlefield pain research, and shape the direction of future research.
On January 10 to 11, 2022, a hybrid in-person and virtual meeting hosted by the US Army Institute of Surgical Research defined research priorities for the Combat Casualty Care Research Program\'s Battlefield Pain research portfolio. Summit participants identified the following key focus areas under the umbrella of battlefield pain research: battlefield injury patterns; use of ketamine and nonopioid analgesics; analgesic delivery systems; the impact of analgesia on performance, cognition, and survival; training methods; battlefield regional anesthesia; and research models. Preliminary statements presented during the summit were refined and rank ordered through a Delphi process.
Consensus was achieved on 7 statements addressing ideal analgesic properties, delivery systems, operational performance concerns, and pain training. Ketamine was identified as safe and effective for battlefield use, and further research into nonopioid analgesics represented a high priority.
The 7 consensus statements that emerged from this battlefield pain summit serve as a template to define the near-term research priorities for military-specific battlefield pain research.

When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD.
In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na+/K+ pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate.
We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na+/K+ ATPase elicits SD. Elevated K+ or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling.
Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory.