Adjuvant Ketamine Research Articles

Patient Controlled Analgesia for Vaso-Occlusive Episodes in Children: A Retrospective Study.

To describe Patient-Controlled Analgesia (PCA) administration in pediatric patients admitted with sickle cell vaso-occlusive episode (VOE). This single-center retrospective study included all inpatient hematology admissions for VOE between 2014 and 2020. PCA-ratio was calculated as the ratio of bolus over continuous IV opioids dose, and time to PCA adjustment as time between first PCA order and a subsequent order that increased dosing or changed opioid medication. A total of 866 encounters (172 unique patients) with PCA for VOE were included. The mean age was 15.4 years old (SD=5.0). On average, after admission (hospital arrival), the first opioid dose was given at 1 hour, PCA started at 3.5 hours, and mean length of stay was 4.3 days (SD=2.5). The mean initial PCA-ratio was 1.7 (SD=0.6). There were no significant associations between age, gender, initial pain score, or admission hemoglobin and PCA-ratio (linear regression model P=0.443). In 24.7% of encounters, the PCA was adjusted within 6 hours. After adjusting by age and gender, lower admission pain scores (OR=1.15, P=0.004), lower PCA-ratio (OR=2.1, P=0.003), longer time to PCA start (OR=1.2, P=0.001), and no adjuvant ketamine (OR=2.4, P < 0.001) were associated with PCA unadjusted within 6 hours. At our institution, patients with VOE received opioids and PCA within the first hours of admission. PCAs were started at a ratio of 1.5-1.8, considered normal continuous. While no specific PCA-ratio was clearly superior for pain control, lower ratios (high continuous infusion) were associated with not requiring PCA adjustments at 6 hours. Prospective studies are needed.

Effects of ADJUVANT Ketamine on Induction of Anesthesia for the Cesarean Section

Effects of ADJUVANT Ketamine on Induction of Anesthesia for the Cesarean Section

Effects of ADJUVANT Ketamine on Induction of Anesthesia for the Cesarean Section.

Effects of ADJUVANT Ketamine on Induction of Anesthesia for the Cesarean Section.

Effects of ADJUVANT Ketamine on Induction of Anesthesia for the Cesarean Section

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Effects of ADJUVANT Ketamine on Induction of Anesthesia for the Cesarean Section

The cesarean section has shown an increasing trend within the past few years. The use of appropriate and effective anesthesia for the procedure is important, not only to reduce the incidence of maternal and fetal morbidities but also to reduce the incidence of intraoperative consciousness. The aim of this study is to evaluate the intraoperative and postoperative effects of adjuvant ketamine, when used in combination with general anesthesia. The study was conducted on the patients referred to Asali hospital for the cesarean section. 100 patients were assigned into two groups. Patients in Group A received thiopental (4 mg / kg) as an anesthetic agent for the surgery, whereas those in group B received thiopental along with 0.5 mg/kg of intravenous ketamine. The effects of ketamine, such as depth of anesthesia, intraoperative and postoperative awareness, vomiting and hallucination were recorded in the questionnaire and data were statistically analyzed using SPSS v25. Of 100 patients in group A, 10 of them were not deeply unconscious. 40 patients in group A and 25 in group B had intraoperative awareness. Depth of anesthesia was significantly associated with the use of ketamine (p = 0.0017) 1 patient in group A and 3 in group B had vomiting and 1 patient in group B was presented with the hallucinations. These parameters were not significantly associated with the dose of ketamine (p = 0.5). Overall use of ketamine is associated with better sedation and no significant side effects, with low doses of ketamine, were seen in our study. Comparative studies using other analgesics, with larger sample size, are therefore recommended.

Ketamine as an Analgesic Adjuvant in Adult Trauma Intensive Care Unit Patients With Rib Fracture.

Rib fracture associated pain is difficult to control. There are no published studies that use ketamine as a therapeutic modality to reduce the amount of opioid to control rib fracture pain. To examine the analgesic effects of adjuvant ketamine on pain scale scores in trauma intensive care unit (ICU) rib fracture. This retrospective, case-control cohort chart review evaluated ICU adult patients with a diagnosis of ≥1 rib fracture and an Injury Severity Score >15 during 2016. Patients received standard-of-care pain management with the physician's choice analgesics with or without ketamine as a continuous, fixed, intravenous infusion at 0.1 mg/kg/h. A total of 15 ketamine treatment patients were matched with 15 control standard-of-care patients. Efficacy was measured via Numeric Pain Scale (NPS)/Behavioral Pain Scale (BPS) scores, opioid use, and ICU and hospital length of stay. Safety of ketamine was measured by changes in vital signs, adverse effects, and mortality. Average NPS/BPS, severest NPS/BPS, and opioid use were lower in the ketamine group than in controls (NPS: 4.1 vs 5.8, P < 0.001; severest NPS: 7.0 vs 8.9, P = 0.004; opioid use: 2.5 vs 3.5 mg morphine equivalents/h/d, P = 0.015). No difference was found between the cohort's length of stay or mortality. Average diastolic blood pressure was higher in the treatment group versus the control group (75.3 vs 64.6 mm Hg, P = 0.014). Low-dose ketamine appears to be a safe and effective adjuvant option to reduce pain and decrease opioid use in rib fracture.

Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial.

Low-dose ketamine has been used perioperatively for pain control and may be a useful adjunct to intravenous (IV) opioids in the control of acute pain in the emergency department (ED). The aim of this study was to determine the effectiveness of low-dose ketamine as an adjunct to morphine versus standard care with morphine alone for the treatment of acute moderate to severe pain among ED patients. A double-blind, randomized, placebo-controlled trial with three study groups was conducted at a large, urban academic ED over a 10-month period. Eligible patients were 18 to 65 years old with acute moderate to severe pain (score of at least 5 out of 10 on the numerical pain rating scale [NRS] and pain duration < 7 days) who were deemed by their treating physician to require IV opioids. The three study groups were: 1) morphine and normal saline placebo (standard care group), 2) morphine and 0.15 mg/kg ketamine (group 1), or 3) morphine and 0.3 mg/kg ketamine (group 2). Participants were assessed at 30, 60, and 120 minutes after study medication administration and received rescue analgesia as needed to target a 50% reduction in pain. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the NRS and calculated as the summed pain-intensity (SPID) difference over 2 hours. The amount and timing of rescue opioid analgesia was evaluated as a secondary outcome. The occurrence of adverse events was also measured. Sixty patients were enrolled (n = 20 in each group). There were no differences between study groups with respect to age, sex, race/ethnicity, preenrollment analgesia, or baseline NRS. Over the 2-hour poststudy medication administration period, the SPIDs were higher (greater pain relief) for the ketamine study groups than the control group (standard care 4.0, interquartile range [IQR] = 1.8 to 6.5; group 1 7.0, IQR = 4.3 to 10.8; and group 2 7.8, IQR = 4.8 to 12.8; p < 0.02). The SPIDs for the ketamine groups were similar (p < 0.46). When compared to standard care, group 2 sustained the reduction in pain intensity up to 2 hours, whereas group 1 was similar to standard care by 2 hours. Similar numbers of patients received rescue analgesia: standard care group, seven of 20, 35%; group 1, four of 20, 20%; and group 2, four of 20, 20% (p = 0.48). Among those receiving rescue analgesia, those in the standard care group received analgesia sooner than either low-dose ketamine group, on average. More participants in the low-dose ketamine groups reported dysphoria and dizziness. Low-dose ketamine is a viable analgesic adjunct to morphine for the treatment of moderate to severe acute pain. Dosing of 0.3 mg/kg is possibly more effective than 0.15 mg/kg, but may be associated with minor adverse events. Future studies should evaluate additional outcomes, optimum dosing, and use in specific populations.

Low‐dose ketamine as a potential adjuvant therapy for painful vaso‐occlusive crises in sickle cell disease

The hallmark of sickle cell disease (SCD) is the acute painful vaso-occlusive crisis (VOC). Among SCD patients, vaso-occlusive pain episodes vary in frequency and severity. Some patients rarely have painful crises, while others are admitted to the hospital multiple times in a year for parenteral analgesics. Opioids are the mainstay of therapy for SCD-related pain. However, a subset of patients report continued pain despite escalating doses of opioids. Tolerance and opioid-induced hyperalgesia (OIH) have been considered as possible explanations for this phenomenon. The activation of the N-methyl-d-aspartate (NMDA) receptor has been implicated in both tolerance and OIH. As a NMDA receptor agonist, ketamine has been shown to modulate opioid tolerance and OIH in animal models and clinical settings. Low-dose ketamine, by virtue of its NMDA receptor agonist activity, could be a useful adjuvant to opioid therapy in patients with refractory SCD-related pain. Based on limited studies of adjuvant ketamine use for pain management, low-dose ketamine continuous infusion appears safe. Further clinical investigations are warranted to fully support the use of low-dose ketamine infusion in patients with SCD-related pain.

Safety and Efficacy of Adjuvant Low-Dose Ketamine Therapy for Patients with Sickle Cell Disease

AbstractAbstract ▪3226▪This icon denotes a clinically relevant abstract Background/Objectives:Opioids are the mainstay of therapy for painful vasoocclusive crises (VOCs) in sickle cell disease (SCD). For some patients, opioid-induced hyperalgesia caused by activation of N-methyl-D-aspartate (NMDA) receptors has been considered to contribute to poor analgesia. Ketamine, an NMDA receptor antagonist, could be a useful adjunct therapy; however safety concerns remain with its use. We examined records of SCD patients at our institution who received ketamine as an adjuvant to opioids at the discretion of anesthesia pain services over the past 4 years. We sought to explore the safety of ketamine and determine its effect on daily opioid requirement in SCD patients hospitalized for VOCs. Methods:The Institutional Review Board at Children's National Medical Center approved this study. A retrospective case-crossover study was conducted through review of the electronic medical record. For each patient we selected 2-paired hospitalizations occurring within 2 years of each other. One hospitalization where the patient received low-dose ketamine infusion in addition to opioid patient controlled analgesia (PCA), and a second hospitalization where the same patient received opioid PCA alone. We compared clinical characteristics of hospitalizations where patients did or did not receive ketamine. Exploratory bivariate analysis (paired t-test and McNemar's test) was used to compare variables between the pairs. Results:Thirty-three patients were identified to have at least 2 hospitalizations for VOC within 20 months of each other where they received adjuvant ketamine infusion during one, while not during the other. Average age was 15.6 ± 3.4 years, 67 % were females, and 36 % were on hydroxyurea therapy. SCD genotypes included homozygous SS 70%, SC 24 %, S-beta-zero thalassemia 3%, and S-beta-plus thalassemia 3%. Mean number of admissions in the 6 months prior to the ketamine hospitalization was 2 (range 0–5) and 64 % had ≥ 2 prior admissions within 6 months. Ketamine dose was 0.1 mg/kg/h for all patients except one who briefly received 0.15 mg/kg/hr. During the ketamine and opioid PCA hospitalization patients reported overall higher pain scores (6.53 vs. 5.94 out of 10; p = 0.0356), required higher doses of opioid (0.0395 mg/kg/hr vs. 0.0323 mg/kg/hr; p = 0.0038), and had a longer length of stay (LOS) (5.6 vs. 4.4 days; p =0.0148) as compared to the PCA alone hospitalization. Patients were more likely to have a diagnosis of acute chest syndrome (ACS) at some point during the ketamine and opioid PCA hospitalization (42% vs. 15 %; p = 0.0126) as compared to the opioid PCA alone hospitalization. Patients were more likely to be treated with additional adjuvant pain control agents (diazepam, lorazepam, gabapentin, pregabalin, amitripyline, or duloxetine) during the ketamine and opioid PCA admission as compared with opioid PCA alone admissions (45% vs. 9% p = 0.0013). Rates of red blood cell transfusion and ICU transfer were not different between the hospitalizations. In 3 patients ketamine was discontinued due to vivid dreams delusions, or dizziness. Nausea, pruritis, sedation, and use of complementary therapies were similar between hospitalizations. Conclusions:We did not observe an opioid sparing effect of ketamine infusion as hypothesized in this group of frequently hospitalized patients. Low-dose ketamine is a safe adjuvant medication for SCD patients hospitalized for VOCs. Higher opioid use during ketamine and opioid PCA admissions is likely due to patients experiencing more severe VOCs as indicated by higher pain scores involving multiple sites, higher rates of ACS, and longer LOS. These severity measures may have contributed to the decision of the pain medicine service to add low-dose ketamine infusion to standard opioid PCA in this retrospective sample. Finally, VOCs in this group of frequently admitted individuals may represent chronic pain which is known to be minimally responsive to most pharmacologic therapies. Patients receiving ketamine appear to be using additional adjuvant pain agents and may be underutilizing hydroxyurea. Prospective randomized studies of adjuvant ketamine therapy in patients with SCD are warranted to determine true efficacy. Disclosures:Off Label Use: Ketamine is a non-barbiturate phencyclidine derivative that is approved for use as a surgical anesthetic. It is not approved for use in pain management, however is commonly used in low-doses as an adjunct to traditional pain control therapies.

Pain management in 100 episodes of severe mucositis in children

We aimed to review the pain management in 100 episodes of severe mucositis in children and determine the incidence of associated side effects. Mucositis is a painful, debilitating condition affecting the alimentary mucosa and occurs following many anticancer treatments. Severe pain associated with mucositis may necessitate reductions, delays or termination of anticancer therapy and so intravenous morphine, preferably by patient-controlled analgesia (PCA) is the treatment of choice. Retrospective review of consecutive episodes of mucositis in children requiring intravenous opioid analgesia over a 3-year period (May 2006-April 2009). In 24/92 (26%) of cases, morphine PCA provided insufficient pain relief and children required adjuvant ketamine therapy. These children had rapidly increasing morphine requirements approaching 1000 mcg/kg/day by day 2 (more than double compared with children on morphine alone), were more likely to be female, and tended to be older (median [IQR] age 12 [6-12] years vs 7 [3-14] years). The addition of ketamine to the morphine PCA appears to be associated with reduced morphine consumption, improved pain scores, causing minimal side effects and no hallucinations. Children with severe mucositis who have escalating morphine requirements may benefit from the addition of ketamine to their morphine PCA.

Efficacy of stellate ganglion block with an adjuvant ketamine for peripheral vascular disease of the upper limbs

Stellate ganglion block (STGB) is commonly indicated in painful conditions like reflex sympathetic dystrophy, malignancies of head and neck, Reynaud’s disease and vascular insufficiency of the upper limbs. The sympathetic blockade helps to relieve pain and ischaemia. Diagnostic STGB is usually performed with local anaesthetics followed by therapeutic blockade with steroids, neurolytic agents or radiofrequency ablation of ganglion. There is increasing popularity and evidence for the use of adjuvants like opioid, clonidine and N Methyl d Aspartate (NMDA) receptor antagonist – ketamine – for the regional and neuroaxial blocks. The action of ketamine with sympatholytic block is through blockade of peripherally located NMDA receptors that are the target in the management of neuropathic pain, with the added benefit of counteracting the “wind-up” phenomena of chronic pain. We studied ketamine as an adjuvant to the local anaesthetic for STGB in 20 cases of peripheral vascular disease of upper limbs during the last 5 years at our institution. STGB was given for 2 days with 2 ml of 2% lignocaine + 8 ml of 0.25% bupivacaine, followed by block with the addition of 0.5 mg/kg of ketamine for three consecutive days. There was significant pain relief of longer duration with significant rise in hand temperature. We also observed complete healing of the gangrenous fingers in 17/19 patients.

Adjuvant ketamine improves cancer pain and has an opioid-sparing effect in paediatric patients

Adjuvant ketamine improves cancer pain and has an opioid-sparing effect in paediatric patients

Ketamine: An Introduction for the Pain and Palliative Medicine Physician

A history of an escalating chronic intractable pain in a patient with cryoglobulinemia, vasculitis, and severe cutaneous ulcerations is presented. A strategy of progressive, multi-agent, N-methyl-D-aspartate-receptor (NMDA-R) blockade that resulted in adequate pain control and a three-fold reduction in opioid consumption is described. Diagnostic process of neuropathic pain and the role of NMDA-R in the development of hyperalgesia are briefly reviewed. Thereafter, existing clinical literature describing the use of Ketamine, a major NMDA-R antagonist for management of malignant pain, is reviewed. Lastly, evidence-based original protocol for intravenous adjuvant Ketamine analgesia for severe cancer pain is presented.

Low-Dose Ketamine in Addition to Propofol for Procedural Sedation and Analgesia in the Emergency Department

To evaluate the efficacy and safety of low-dose intravenous ketamine in addition to intravenous propofol for procedural sedation and analgesia in the emergency department (ED). Articles were identified using PubMed (1949-February 2007), MEDLINE (1966-February 2007), EMBASE (1980-February 2007), BioMed Central (to February 2007), the Cochrane Library (to February 2007), International Pharmaceutical Abstracts, and Google Scholar (until February 2007). Reference citations from retrieved publications were also reviewed. Search terms included ketamine, propofol, ketamine-propofol, ketofol, combination, sedation, procedural sedation, conscious sedation, and emergency department. All articles on prospective procedural sedation that were published or translated into English and that compared combination ketamine-propofol with an appropriate comparator group were included. Clinically relevant safety endpoints included the frequency of significant hemodynamic and respiratory compromise warranting medical intervention, nausea, vomiting, and emergence reactions. Time until hospital discharge criteria were met and patient satisfaction scores were efficacy endpoints of interest. Of the 11 trials included in this review, most had small sample sizes and were conducted in non-ED settings. The ketamine-propofol combination demonstrated no additional efficacy over propofol in terms of time to discharge. Although fewer patients given the ketamine-propofol combination experienced significant hemodynamic and respiratory compromise, need for active interventions, including fluid or vasopressor administration, supplemental oxygen, or assisted ventilation did not differ between groups. Patients who received higher doses of adjuvant ketamine reported an increased incidence of nausea, vomiting, and emergence reactions following the procedure. Few studies reported patient satisfaction scores postprocedure, and effect of ketaminepropofol on time-to-discharge criteria met was inconclusive. At this time, insufficient clinical evidence exists to recommend the routine use of low-dose ketamine with propofol for procedural sedation in the ED setting.

Ketamine as an adjuvant to opioids for cancer pain.

Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of cancer pain, particularly when opioids alone prove to be ineffective. Ketamine is known to have hallucinogenic side effects. To date no systematic review of the benefits and harms of adjuvant ketamine for cancer pain has been undertaken. To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids in the treatment of cancer pain. Studies were identified from MEDLINE (1966-2001), EMBASE (1980-2001), CancerLit (1966-2001), the Cochrane Library (Issue 1, 2001); by handsearching reference lists from review articles, trials, and chapters from standard textbooks on pain and palliative care. The manufacturer of ketamine (Pfizer Parke-Davis) provided search results from their in-house database, PARDLARS. RCTs of adult patients with cancer and pain being treated with an opioid, and receiving either ketamine (any dose and any route of administration) or placebo or an active control. Two independent reviewers identified four RCTs for possible inclusion in the review, and 32 case studies/case series reports. Quality and validity assessment was performed by three independent reviewers, and two RCTs were excluded because of inappropriate study design. Patient reported pain intensity and pain relief was assessed using visual analog scales, verbal rating scales or other validated scales, and adverse effects data were collated. Two trials were eligible for inclusion in the review and both concluded that ketamine improves the effectiveness of morphine in the treatment of cancer pain. However, pooling of the data was not appropriate because of the small total number of patients (30), and the presence of clinical heterogeneity. Some patients experienced hallucinations on both ketamine plus morphine and morphine alone and were treated successfully with diazepam. No other serious adverse effects were reported. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of cancer pain. More randomized controlled trials are needed.

Patient-controlled bupivacaine wound instillation following cesarean section: the lack of efficacy of adjuvant ketamine

Study objective To assess the analgesic efficacy of ketamine when administered as an adjuvant to bupivacaine for patient-controlled wound instillation following cesarean section. Study design Prospective, randomized, double-blind study. Setting Large referral hospital. Patients 50 term parturients undergoing cesarean section. Interventions In all cases, a standard spinal anesthetic was administered. On completion of the surgery, a multihole 20 G epidural catheter (B. Braun, Melsungen, Germany) was placed above the fascia such that the tip was sited at the point which demarcated 50% of the length of the surgical wound. Thereafter, the catheter was connected to a patient-controlled drug delivery device. The device was filled with either 0.125% bupivacaine (bupivacaine group) or 0.125% bupivacaine and ketamine (1 mg/mL) (bupivacaine-ketamine group). Postoperatively, wound instillation was performed via the patient-controlled analgesia device. During the first 6 postoperative hours, a co-investigator administered “rescue” morphine (2 mg IV). Thereafter, “rescue” dipyrone (1 g) was administered on patient request. Measurements and main results At all time intervals, visual analog scale (VAS) for pain at rest, on coughing, and during leg raise were similar between the groups. All patients (100%) in both treatment groups received “rescue” morphine. Similarly, the number of doses of 2 mg “rescue” morphine administered was unaffected by patient randomization. The total “rescue” morphine administered during the first 6 postoperative hours was 11.2 ± 4.6 mg versus 11.3 ± 5.6 mg for the bupivacaine group and bupivacaine-ketamine group, respectively. The number of pump infusions during the 24-hour study period was 9 ± 2 and 9 ± 3 for the bupivacaine group and bupivacaine-ketamine group, respectively. The volume infused via the delivery device was similar between the groups (81 ± 18 mL vs. 85 ± 24 mL for the bupivacaine group and bupivacaine-ketamine group, respectively). Psychomental and cognitive function as measured by the Digit Symbol Substitution and Mini Mental Tests were unaffected by adjuvant ketamine administration. Patient satisfaction was similar between the groups. Conclusion Adjuvant local ketamine does not enhance bupivacaine-induced wound instillation following cesarean section.