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Sixty unpremedicated outpatients undergoing elective extracorporeal shock wave lithotripsy using an unmodified Dornier HM-3 lithotriptor were randomly assigned to receive an intravenous infusion of either alfentanil or ketamine as an adjuvant to midazolam for sedation and analgesia. Although both drug regimens allowed the maximal number of shock waves and energy level, the alfentanil group had significantly better calculi fragmentation (78% vs. 50% of patients with fragments less than 2 mm). Ketamine infusion provided superior intraoperative cardiorespiratory stability; however, it was associated with more disruptive movements (22 vs. 5) and dreaming (35% vs. 5%) during the procedure (P less than 0.05). Postoperatively, confusion also occurred more frequently in the ketamine-treated patients (31% vs. 5%, P less than 0.05). Alfentanil infusion was associated with more episodes of hemoglobin oxygen desaturation to less than 90% (12 vs. 2, P less than 0.05), itching (23% vs. 4%, P less than 0.05), and ability to recall intraoperative events (45% vs. 12%, P less than 0.05). The incidence of postoperative nausea was decreased (not significantly) in the alfentanil group (32% vs. 54%). The mean anesthesia time was similar in both groups; however, discharge times (means +/- standard deviations) were shorter in the alfentanil group (142 +/- 42 min vs. 161 +/- 31 min, P = 0.05). These data suggest that although both techniques proved effective for anesthesia in outpatients undergoing immersion lithotripsy, alfentanil is superior to ketamine as part of a sedative-analgesic technique because of the improved recovery profile and calculi fragmentation.
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PMID:Comparison of alfentanil and ketamine infusions in combination with midazolam for outpatient lithotripsy. 204 57

Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation ("empty head") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.
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PMID:Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. 1102 5

Sedatives continue to be used on a routine basis in critically ill patients. Although many agents are available and some approach an ideal, none are perfect. Patients require continuous reassessment of their pain and need for sedation. Pathophysiologic abnormalities that cause agitation, confusion, or delirium must be identified and treated before unilateral administration of potent sedative agents that may mask potentially lethal insufficiencies. The routine use of standardized and validated sedation scales and monitors is needed. It is hoped that reliable objective monitors of patients' level of consciousness and comfort will be forthcoming. Each sedative agent discussed in this article seems to have a place in the ICU pharmacologic armamentarium to ensure the safe and comfortable delivery of care. Etomidate is an attractive agent for short-term use to provide the rapid onset and offset of sedation in critically ill patients who are at risk for hemodynamic instability but seem to need sedation or anesthesia to perform a procedure or manipulate the airway. Ketamine administered through intramuscular injection or intravenous infusion provides quick, intense analgesia and anesthesia and allows patients to tolerate limited but painful procedures. The risk/benefit ratio associated with the use of this neuroleptic agent must be weighed carefully. Ketamine is contraindicated in patients who lack normal intracranial compliance or who have significant myocardial ischemia. Barbiturates are reserved mainly to induce coma in patients at risk for severe CNS ischemia, which frequently is associated with refractory intracranial hypertension, or in patients with status epilepticus. When administered in high doses, these drugs have prolonged sedative and depressant effects. Judicious hemodynamic monitoring is required when barbiturate coma is induced. Haloperidol is indicated in the treatment of delirium. Patients should be monitored for extrapyramidal side effects and, when they require higher doses, for potential electrocardiographic prolongation of the QT interval. Dexmedetomidine may evolve into an agent with qualities comparable with midazolam and propofol, and it may even become a drug of choice in select patients. Further study is required, however. Propofol has many of the qualities of an ideal sedative agent. Benzodiazepines and narcotics often are used in concert with propofol to provide reliable amnesia and to relieve pain, respectively. Propofol frequently causes hypotension when administered as a bolus or infusion, particularly in patients with limited cardiac reserve or hypovolemia. More data must be obtained to identify potential deleterious effects of hypertriglyceridemia, and further evaluation of the potential benefits in certain patient populations, such as neurosurgical patients, is needed.
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PMID:Use of propofol and other nonbenzodiazepine sedatives in the intensive care unit. 1176 65

The abuse of methylenedioxymethamphetamine (MDMA), flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate (GHB) is discussed. Club drugs are chemical substances used recreationally in social settings. Use is increasingly frequent among young people, especially during all-night dance parties. All four agents have been classified as controlled substances. MDMA ("ecstasy") is available as a tablet, a capsule, and a powder; formulations may contain many adulterants. MDMA increases the release of neurotransmitters. The desired effects are euphoria, a feeling of intimacy, altered visual perception, enhanced libido, and increased energy. The most common adverse effects are agitation, anxiety, tachycardia, and hypertension. More serious adverse effects include arrhythmias, hyperthermia, and rhabdomyolysis. Flunitrazepam is a potent benzodiazepine. At higher doses, the drug can cause lack of muscle control and loss of consciousness. Other adverse effects are hypotension, dizziness, confusion, and occasional aggression. Ketamine is a dissociative anesthetic used primarily in veterinary practice. It may be injected, swallowed, snorted, or smoked. Like phencyclidine, ketamine interacts with the N-methyl-D-aspartate channel. Analgesic effects occur at lower doses and amnestic effects at higher doses. Cardiovascular and respiratory toxicity may occur, as well as confusion, hostility, and delirium. GHB, a naturally occurring fatty acid derivative of gamma-aminobutyric acid, was introduced as a dietary supplement. Increasing doses progressively produce amnesia, drowsiness, dizziness, euphoria, seizures, coma, and death. Flunitrazepam, ketamine, and GHB have been used to facilitate sexual assault. Supportive care is indicated for most cases of club drug intoxication. The increasing abuse of MDMA, flunitrazepam, ketamine hydrochloride, and GHB, particularly by young people in social settings such as clubs, should put health care professionals on guard to recognize and manage serious reactions.
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PMID:Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate. 1206 92

A 22-year-old woman presenting with postpartum haemorrhagic shock at 4243 m altitude required anaesthesia to identify and treat the source of bleeding. Slow intravenous administration of ketamine (0.5 mg x kg(-1)) resulted in deep anaesthesia and apnoea requiring hand ventilation for 5 min. Haemodynamic stability was maintained throughout the procedure. Haemostasis was achieved following uterine packing and suture of a second-degree vaginal tear and small cervical tear. Confusion and visual hallucinations occurred upon awakening but recovery was otherwise uneventful. Ketamine can be used for emergency anaesthesia in a wilderness environment over 4000 m but it is probable that the benefits outweigh the risks only where life or limb are acutely threatened. Careful titration of the administered dose is strongly advised, particularly in patients where hypovolaemia and/or hypoxaemia are present. The availability of airway management equipment and the skills to use them may significantly reduce the risks associated with anaesthetic administration at very high altitude.
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PMID:Ketamine for emergency anaesthesia at very high altitude (4243 m above sea-level). 1808 87

Ketamine has been the commonest abusive substance used by Hong Kong teenager since 2005. It is also the fourth commonest poison encountered in Hong Kong Poison Information Centre (HKPIC) poisoning data in 2010. From June 2008 to July 2011, HKPIC managed 188 and 96 cases of acute and chronic ketamine poisoning, respectively, which reflect its acute and chronic toxicity pattern. Demographically, there is a male predominance, and the majority is between the ages of 10-39. For the acute cases, 48 % presented with neurological features such as confusion, drowsiness, or transient loss of consciousness which usually subside with supportive care in a few hours. For the chronic cases, 92 % of them presented with features of ketamine cystitis while about 66 % presented with chronic abdominal pain. The current understanding of ketamine cystitis and chronic abdominal pain will be reviewed. Management is primarily symptomatic measures and most importantly abstinence from ketamine use.
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PMID:Acute and chronic toxicity pattern in ketamine abusers in Hong Kong. 2255 37

Many common elective surgeries are associated with moderate-to-severe postoperative pain. These common surgeries include total knee and total hip arthroplasty, thoracotomy, and multilevel lumbar spine surgery. Unfortunately, many patients requiring these surgeries are already in moderate-to-severe pain, necessitating high doses of oral or transdermal opioids preoperatively. This is an established risk factor for difficult-to-control postoperative pain.(1,2) Opioid-sparing interventions are important elements in these patients to promote convalescence and reduce common opioid side effects such as constipation, confusion, pruritus, nausea, vomiting, and urinary retention. Potential interventions to reduce postoperative pain can include nonsteroidal anti-inflammatory drugs, acetaminophen, gabapentin, and even invasive therapies such as epidural or peripheral nerve blockade. Ketamine is a well-known anesthetic agent that has opioid-sparing analgesic properties, is noninvasive, and in analgesic doses, has few contraindications. This article will review the basic science behind ketamine, some of the evidence supporting its perioperative use, and the logistics of how the Department of Anesthesia at Mayo Clinic in Jacksonville, Florida rolled out a hospital-wide ketamine infusion protocol.
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PMID:Perioperative ketamine for acute postoperative analgesia: the Mayo Clinic-Florida experience. 2600 64

Since its discovery, ketamine, a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist related to phencyclidine, has been linked to multiple adverse reactions sometimes described as "out of body" and "near death experiences," including emergence phenomena, delusions, hallucinations, delirium, and confusion. Due to these effects, ketamine has been withdrawn from mainstream anesthetic use in adult patients. Evoked potentials (EPs) are utilized to monitor neural pathways during surgery, detect intraoperative stress or damage, detect and define the level of neural lesions, and define abnormalities. Unfortunately, many of the volatile anesthetics commonly used during spinal and neurologic procedures suppress EP amplitude and monitoring. Ketamine has been found in several preclinical and clinical studies to actually increase EP amplitude and thus has been used as an analgesic adjunct in procedures where EP monitoring is critical. Once the gap in our knowledge of ketamine's risks has been sufficiently addressed in animal models, informed clinical trials should be conducted in order to properly incorporate ketamine-based anesthetic regimens during EP-monitored neurosurgeries.
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PMID:Ketamine-Based Anesthetic Protocols and Evoked Potential Monitoring: A Risk/Benefit Overview. 2690 17

Excited delirium syndrome (ExDS) is defined by marked agitation and confusion with sympathomimetic surge and incessant physical struggle, despite futility, which may lead to profound pathophysiologic changes and sudden death. Severe metabolic derangements, including lactic acidosis, rhabdomyolysis, and hyperthermia, occur. The pathophysiology of excited delirium is a subject of ongoing basic science and clinical research. Positive associations with ExDS include male gender, mental health disorders, and substance abuse (especially sympathomimetics). Excited delirium syndrome patients often exhibit violent, psychotic behavior and have "superhuman" strength which can result in the patient fighting with police and first responders. Continued struggle can cause a patient with ExDS to experience elevated temperature (T) and acidosis which causes enzymes to fail, leading to sudden death from cardiovascular collapse and multi-system organ failure. Therefore, effective early sedation is optimal to stop this fulminant process. Treatment of ExDS must be focused on rapidly, safely, and effectively sedating the patient and providing intensive, supportive care. Benzodiazepines, like midazolam, may not be ideal to sedate ExDS patients since their onset takes several minutes, and their side effects include loss of airway control and respiratory depression. Injectable antipsychotic medications have a relatively slow onset and may cause prolongation of the QTc interval. Ketamine is the ideal medication to sedate patients with ExDS. Ketamine has a rapid, predictable onset within three to four minutes when given by intramuscular (IM) injection. It does not adversely affect airway control, breathing, heart rate, or blood pressure (BP). In this retrospective case series, prehospital scenarios in which ExDS patients received ketamine by paramedics for sedation, and their subsequent treatment in the emergency department (ED) and hospital, are described. It is demonstrated that ketamine administered by paramedics in the prehospital setting of a community hospital based Emergency Medical Services (EMS) system is a safe and effective treatment for ExDS. Scaggs TR , Glass DM , Hutchcraft MG , Weir WB . Prehospital ketamine is a safe and effective treatment for excited delirium in a community hospital based EMS system. Prehosp Disaster Med. 2016;31(5):563-569.
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PMID:Prehospital Ketamine is a Safe and Effective Treatment for Excited Delirium in a Community Hospital Based EMS System. 2751 1

BackgroundKetamine has emerged as a novel therapeutic agent for major depressive episodes, spurring interest in its potential to augment electroconvulsive therapy (ECT).AimsWe sought to update our preliminary systematic review and meta-analysis, focusing on randomised controlled trials (RCTs) involving an index course of ECT, and testing the hypothesis that lack of efficacy is due to barbiturate anaesthetic co-administration.MethodWe searched EMBASE, CENTRAL and Medline to identify RCTs examining the efficacy of ketamine during a course of ECT. Data were synthesised from ten trials (ketamine group n = 333, comparator group n = 269) using pooled random effects models.ResultsElectroconvulsive therapy with ketamine was not associated with greater improvements in depressive symptoms or higher rates of clinical response or remission, nor did it result in pro-cognitive effects. This held true when limiting analysis to trials without barbiturate anaesthetic co-administration. Increased rates of confusion were reported.ConclusionsOverall, our analyses do not support using ketamine over other induction agents in ECT.
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PMID:Adjunctive ketamine in electroconvulsive therapy: updated systematic review and meta-analysis. 2948 19


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