Intravenous ketamine as an analgesia in prehospital adult trauma patients

Background: Prehospital traumatic pain is common, but the quality of pain management in these patients is poor. Current practice recommends morphine as the first-line analgesia in major trauma but this carries high risks and is often contraindicated. Alternative paramedic-administered analgesia does not provide adequate pain relief or may be contraindicated. As a result, many patients remain in pain. Analgesic ketamine is used safely and effectively in international civilian and military settings and by paramedics with additional training, education and qualifications. Aim: The study had two aims. Namely, these were to find out whether intravenous ketamine: provides effective relief of prehospital traumatic pain in adults; and is safe for prehospital administration by non-specialist paramedics. Method: Three databases, CINAHL, MEDLINE and AMED, were searched to identify articles published between 2009 and 2021. Exclusion criteria were applied and results subjected to critical appraisal and evaluation. Findings: Four studies were included in the review. Two themes were identified for thematic analysis: therapeutic effectiveness; and the safety of IV ketamine administration by paramedics. The evidence drew predominantly homogenous conclusions, but was substandard regarding external validity, which limited the quality of these conclusions. Conclusion: Ketamine provides effective pain relief in line with morphine and is safe for paramedics to administer. However, clear gaps in the evidence mean the research questions are not fully answered, so changes to current paramedic practice cannot be recommended.

Association of VEGF With Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Treatment-Refractory Depression

Objectives: To first explore the role of plasma vascular endothelial growth factor (VEGF) concentrations in ketamine's antianhedonic effects, focusing on Chinese patients with treatment-refractory depression (TRD).Methods: Seventy-eight patients with treatment-refractory major depressive disorder (MDD) or bipolar disorder (BD) were treated with six ketamine infusions (0.5 mg/kg). Levels of anhedonia were measured using the Montgomery–Åsberg Depression Rating Scale (MADRS) anhedonia item at baseline, day 13 and 26. Plasma VEGF concentrations were examined at the same time points as the MADRS.Results: Despite a significant reduction in anhedonia symptoms in individuals with treatment-refractory MDD (n = 59) or BD (n = 19) after they received repeated-dose ketamine infusions (p < 0.05), no significant changes in plasma VEGF concentrations were found at day 13 when compared to baseline (p > 0.05). The alteration of plasma VEGF concentrations did not differ between antianhedonic responders and non-responders at days 13 and 26 (all ps > 0.05). Additionally, no significant correlations were observed between the antianhedonic response to ketamine and plasma VEGF concentrations (all ps > 0.05).Conclusion: This preliminary study suggests that the antianhedonic effects of ketamine are not mediated by VEGF.

Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review

Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions.

Intravenous ketamine for rapid treatment of major depressive disorder in the general medical hospital

Major depressive disorder (MDD) is common in general medical settings, and can usually be treated with conventional oral antidepressants. For some patients, however, oral treatment is refused or not possible, and the untreated symptoms can have a significant impact on the treatment of the acute medical problem. Use of intravenous ketamine has been widely reported in mental health settings for the treatment of MDD. We describe use of intravenous ketamine in a general medical hospital for the treatment of MDD in an 83-year-old male patient who refused food, fluid and medical investigations following a stroke.

‘NOPAIN-ROP’ trial: Intravenous fentanyl and intravenous ketamine for pain relief during laser photocoagulation for retinopathy of prematurity (ROP) in preterm infants: A randomised trial

ObjectivesTo investigate if intravenous fentanyl or intravenous ketamine can provide adequate analgesia in preterm infants undergoing laser photocoagulation for retinopathy of prematurity (ROP).DesignOpen-label randomised trial.SettingTertiary care institution.ParticipantsPreterm infants who underwent laser photocoagulation for ROP.InterventionsInfants were randomised to receive fentanyl as intravenous bolus dose of 2 µg/kg, followed by an intravenous infusion of 1 µg/kg/hour increased to a maximum of 3 µg/kg/hour or intravenous ketamine as bolus dose of 0.5 mg/kg, followed by further intermittent intravenous bolus doses of 0.5 mg/kg to a maximum of 2 mg/kg in the initial phase and intravenous fentanyl (bolus of 2 µg/kg followed by infusion of 2 µg/kg/hour to a maximum of 5 µg/kg/hour) or intravenous ketamine (bolus dose of 1 mg/kg followed by intermittent bolus doses of 0.5 mg/kg to a maximum of 4 mg/kg) in the revised regimen phase.Main outcome measuresProportion of infants with adequate analgesia defined as the presence of both: (1) all the Premature Infant Pain Profile-Revised scores measured every 15 min less than seven and (2) proportion of the procedure time the infant spent crying less than 5%.Secondary outcomes included apnoea, cardiorespiratory or haemodynamic instability, feed intolerance and urinary retention requiring catheterisation during and within 24 hours following the procedure.ResultsA total of 97 infants were randomised (fentanyl=51, ketamine=46). The proportions of infants with adequate analgesia were 16.3% (95% CI 8.5% to 29%) with fentanyl and 4.5% (95% CI 1.3% to 15.1%) with ketamine. Ten infants (19.6%) in the fentanyl group and seven infants (15.2%) in the ketamine group had one or more side effects. In view of inadequate analgesia with both the regimens, the study steering committee recommended using a higher dose of intravenous fentanyl and intravenous ketamine. Consequently, we enrolled 27 infants (fentanyl=13, ketamine=14). With revised regimens, the proportions of infants with adequate analgesia were higher: 23.1% (95% CI 8.2% to 50.2%) with fentanyl and 7.1% (95% CI 1.3% to 31.5%) with ketamine. However, higher proportions of infants developed apnoea (n=4; 30.7%), need for supplemental oxygen (n=5, 38.4%) and change in cardiorespiratory scores (n=7; 53.8%) with fentanyl but none with ketamine.ConclusionsFentanyl-based and ketamine-based drug regimens provided adequate analgesia only in a minority of infants undergoing laser photocoagulation for ROP. More research is needed to find safe and effective regimens that can be employed in resource constrained settings.Trial registration numberCTRI/2018/03/012878.