Low-dose Infusion Research Articles

Bolus-free low-dose levosimendan infusion for acute decompensated hypoperfused heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Aims and Methods Aim of this study was to assess the feasibility of a bolus-free, low-dose levosimendan infusion for acute decompensated heart failure (ADHF) with hypoperfusion. All consecutive patients who received levosimendan without intravenous bolus at our Department for ADHF in the last 6 months were included in this is a single-center retrospective study. To avoid abrupt drop in blood pressure, all patients started infusion at 0.01 mcg/kg/min, and gradual titration was achieved, up to 0.1 mcg/kg/min. Continuous variables are reported as medians (IQR), categorical as proportions. Paired measures were compared with the Wilcoxon signed-rank test. p-value was set at 5%. Analyses were performed using RStudio v1.3. Results We included 26 patients [males 84.6%; age 72 (59-76) years]. Patients had severe LV dysfunction [LVEF of 20 (20-25)%] and moderate/severe RV dysfunction in 46.2%. Most patients were admitted for cardiogenic shock (26.9%) or low-output state (61.5%); baseline serum lactate was 1.6 (1.2-3.2) mmol/L. Etiology was ACS in 26.9% patients, worsening HF in 53.8%, and valvular disease in 26.9%. All patients required inotropes: 73.1% required adrenaline [max dose 0.10 (0.05-0.15) mcg/kg/min]; 50.0% required noradrenaline [max dose 0.10 (0.05-0.18) mcg/kg/min]; 26.9% received levosimendan alone [max dose 0.05 (0.03-0.10) mcg/kg/min]. Levosimendan was used in combination with adrenaline in 69.2%, after 3 (0-4) days of adrenaline initiation. Duration of levosimendan infusion was 3 (1-4) days. MCS was pursued in 69.2% [57.7% IABP, 15.4% Impella CP, and 3.8% VA-ECMO]. Oro-tracheal intubation was required in 50.0%, CVVHDF was required in 11.5% patients. No patient required levosimendan interruption for hypotension/arrhythmia. In-hospital mortality was 7.7%. One patients underwent successful LVAD implantation, and one patient was referred for HTx. Invasive hemodynamic data, before and during levosimendan, was available for 7 patients. Initiation of levosimendan led to a non-significant drop in SVR [14.8 (13.3-16.9) vs 19.5 (14.6-25.4) WU; p = 0.093], but SBP was unchanged (p = 0.470). Left ventricular systolic performance was improved: CI [2.6 (2.4-2.7) vs 2.2 (2.0-2.3) Lt/min/m²; p = 0.016]; CPO [0.9 (0.8-1.0) vs 0.8 (0.8-0.9) W; p = 0.031]. Mean PAP (p = 0.297), and PCWP (p = 0.149) remained unchanged. Notably, no significant adjustments in diuretic (p = 0.422) or adrenaline (p = 0.999) doses, IABP counterpulsation ratio (p = 0.999), or Impella flow (p = 0.999) were recorded between these longitudinal assessments. As a result of improved myocardial function, LVEF increased from admission to discharge [20 (20-25) vs 25 (20-32)%; p = 0.024]. Discussion This preliminary study reports on a bolus-free, low-intensity levosimendan regimen for ADHF with hypoperfusion. Levosimendan improved indexes of myocardial performance. In this cohort, levosimendan often required concomitant inopressor and was started at a very low dose to avoid abrupt drop in blood pressure. Abstract Figure 1

A phase II study of human allogeneic liver-derived progenitor cell therapy for acute-on-chronic liver failure and acute decompensation

Background & AimsHuman allogeneic liver-derived progenitor cells (HALPC, HepaStem®; Promethera Biosciences, Mont-Saint-Guibert, Belgium) are an advanced therapy medicinal product that could potentially alleviate systemic inflammation and ameliorate liver function in patients with acute-on-chronic liver failure (ACLF) or acute decompensation of cirrhosis (AD).MethodsThis open-label phase II study was conducted in 9 centres in Belgium, Spain, and Bulgaria between 2016 and 2019. The primary objective was to assess the safety of HALPC therapy up to Day 28 and the secondary objectives were to assess its safety and preliminary efficacy up to Month 3.ResultsThe 24 treated patients (mean age: 51 years) were mostly male with an alcoholic cirrhosis. On pre-infusion Day 1, 15 patients had ACLF and 9 patients had AD. Two of the 3 initial patients treated with high HALPC doses (∼5×106 cells/kg body weight [BW]) had severe adverse bleeding events attributed to treatment. In 21 patients subsequently treated with lower HALPC doses (0.6 or 1.2×106 cells/kg BW, 1 or 2 times 7 days apart), no serious adverse events were related to treatment, and the other adverse events were in line with those expected in patients with ACLF and AD. Overall, markers of systemic inflammation and altered liver function decreased gradually for the surviving patients. The Day-28 and Month-3 survival rates were 83% (20/24) and 71% (17/24), and at Month 3, no patient had ACLF.ConclusionsThe treatment of patients with ACLF or AD with up to 2 doses of 1.2×106 HALPC/kg BW appeared safe. The results of this study support the initiation of a proof-of-concept study in a larger cohort of patients with ACLF to further confirm the safety and evaluate the efficacy of HALPC therapy.Clinical Trials RegistrationEudraCT 2016-001177-32.Lay summaryPatients with liver cirrhosis may suffer from the rapid onset of organ failure or multiple organ failure associated with a high risk of death in the short term. This clinical study of 24 patients suggests that an advanced therapy based on the intravenous infusion of low doses of human allogeneic liver-derived progenitor cells is safe and supports the next phase of clinical development of this type of therapy.

Reasons for discontinuation of acute postoperative pain ketamine infusions: A retrospective case-control study.

The purpose of the study was to investigate factors associated with early discontinuation of low-dose ketamine infusions due to adverse drug events (ADEs). A retrospective, matched case-control study of surgical patients who received low-dose ketamine infusions for postoperative pain over 6years was conducted. Forty-seven study patients, who required early discontinuation of their infusion due to ADEs, were included and matched 1:1 with 47 controls, who did not experience ADEs, for a total of 94 patients. The two groups were compared based on surgery type, American Society of Anesthesiologists (ASA) classification, administration of specific perioperative anxiolytic, anesthetic, and analgesic medications, and use of regional anesthesia. Of the study patients, 44.7% underwent spine procedures (vs. 34% of controls), 27.6% underwent abdominal procedures (vs. 8.5% of controls), 19.2% underwent orthopedic procedures (vs. 46.8% of controls), and 8.5% underwent thoracic procedures (vs. 6.4% of controls). There were no statistically significant differences in ASA classification, pre-operative gabapentinoid and antidepressant use, average ketamine infusion dose, or postoperative use of peripheral nerve catheters, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, muscle relaxants, and nonbenzodiazepine sleep aides. Study patients had higher rates of intra-operative volatile anesthetic use (78.7% vs. 57.7%, p=0.03) and more postoperative opioid patient-controlled analgesia (PCA) use (53.2% vs. 29.8%, p=0.02) than controls. Control patients had higher rates of preoperative opioid use (76.7% vs. 53.2%, p=0.02) and premedication with midazolam (89.4% vs. 70.2%, p=0.02) than study patients. Patients who required discontinuation of their low-dose ketamine infusion due to ADEs were more likely to be opioid naïve, received less pre-operative benzodiazepines, and had greater postoperative opioid PCA requirements. Control patients, on the other hand, had higher rates of pre-operative opioid use and experienced fewer ADEs despite greater total ketamine doses.

Combined therapy of mesenchymal stem cells with a GLP-1 receptor agonist, liraglutide, on an inflammatory-mediated diabetic non-human primate model

AimsImmunomodulation concurrent with the promotion of β-cell function is a strategy used to develop innovative therapies for type 1 diabetes (T1D). Here, we assessed the therapeutic potential of co-administration of human clonal mesenchymal stem (stromal) cells (hBM-cMSCs) and liraglutide as a glucagon-like peptide-1 agonist in a non-human primate model with streptozotocin (STZ)-induced diabetes. Main methodsDiabetes was induced through intravenous (i.v.) multiple low-dose (MLD) infusions of STZ at a dose of 30 mg/kg body weight (b.w.) for five consecutive days, followed by two booster injections of 35 mg/kg on days 12 and 19. After 90 days, the diabetic animals were randomly allocated to two groups: The combination therapy group (n = 4) received injections of 1.5 × 106 hBM-cMSCs/kg b.w. through celiac artery by angiography on days 91 and 105 and daily subcutaneous injections of liraglutide (up to 1.8 mg/day) until day 160 while vehicle group received phosphate-buffered saline. The monkeys were assessed for functional, immunological, and histological analysis. Key findingsThe combined treatment group had continued reduction in FBG levels up to day 160, which was accompanied by increased b.w., C-peptide, and β-cell function, and decreased HbA1c and fructosamine levels compared to vehicle group. The combined treatment increased Tregs, IL-4, IL-10, and TGF-β1 and decreased IL-6 and IL-1β. Stereological analysis of the pancreatic tissue exhibited more total volume of insulin-secreting islets in the combined treatment group compared to vehicle group. SignificanceOur findings demonstrated this combined treatment impaired the clinical symptoms of diabetes in this animal model through immunomodulation and β-cell preservation.

Activation of the Cholinergic Anti-inflammatory Pathway Attenuated Angiotension II-Dependent Hypertension and Renal Injury.

Background: Angiotensin II (AngII) induces renal fibrosis, characterized by fibroblast proliferation, inflammatory cell infiltration and excessive extracellular matrix deposition, all of which was relevant closely to hypertension. The vagus nerve-related cholinergic anti-inflammatory pathway (CAP) modulates local and systemic inflammatory responses. The aim of present study was to determine the effect of CAP on renal inflammation and fibrosis. Methods and Results: AngII-induced hypertension was induced in vivo by 14-days low-dose AngII infusion from osmotic minipumps. We used GTS-21 dihydrochloride, a selective nicotinic acetylcholine receptor agonist. Daily intraperitoneal GTS-21 injection and/or vagotomy started after hypertension was confirmed and continued for 4 weeks. The elevated blood pressure caused by AngII was significantly attenuated by GTS-21. Improved baroreflex sensitivity was observed after GTS-21 administration. Masson stain and immunoblotting revealed that deposition of excessive fibrosis and overexpression of inflammatory cytokines induced by AngII was reduced by GTS-21. To determine the role of autonomic control in CAP, unilateral vagotomy was performed. Vagotomy weakened the effect of CAP on AngII-induced hypertension. In vitro, GTS-21 suppressed NF-κB activation, attenuated AngII-induced epithelial-mesenchymal transition and reduced inflammation and fibrosis in NRK-52E cells; α-bungarotoxin (α-Bgt, an α7-nAChR selective antagonist) partly inhibited these effects. Conclusion: CAP protected against AngII-induced hypertension via improvement in autonomic control, suppression of NF-κB activation, and reduction of renal fibrosis and inflammatory response.

Mechanical Prosthetic Aortic Valve Thrombosis Treated with Low-dose Ultra Slow Infusion of Tissue-type Plasminogen Activator during Pregnancy.

Mechanical Prosthetic Aortic Valve Thrombosis Treated with Low-dose Ultra Slow Infusion of Tissue-type Plasminogen Activator during Pregnancy.

Low-Dose Intravenous Heparin Infusion After Aneurysmal Subarachnoid Hemorrhage is Associated With Decreased Risk of Delayed Neurological Deficit and Cerebral Infarction.

Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000U, 3×daily). To assess the safety and efficacy of LDIVH in aSAH patients. We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome data were compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW). The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9vs 18%; P=.004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTW showed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts. This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.

Commentary: Low-Dose Intravenous Heparin Infusion After Aneurysmal Subarachnoid Hemorrhage Is Associated With Decreased Risk of Delayed Neurological Deficit and Cerebral Infarction.

Commentary: Low-Dose Intravenous Heparin Infusion After Aneurysmal Subarachnoid Hemorrhage Is Associated With Decreased Risk of Delayed Neurological Deficit and Cerebral Infarction.

Low-Dose (0.05 Unit/kg/hour) vs Standard-Dose (0.1 Unit/kg/hour) Insulin in the Management of Pediatric Diabetic Ketoacidosis: A Randomized Double-Blind Controlled Trial

To compare the efficacy of insulin infusion of 0.05 Unit/kg/hour vs 0.1 Unit/kg/hour in the management of pediatric diabetic ketoacidosis (DKA). Randomized, double-blind controlled clinical trial. Pediatric critical care division of a tertiary care hospital from October, 2014 to July, 2018. Children aged 12 years or younger with a diagnosis of DKA. Children with septic shock and those who had received insulin before enrollment were excluded. Low-dose (0.05 Unit/kg/hour) vs. Standard-dose (0.1 Unit/kg/hour) insulin infusion. The primary endpoint was time for resolution of DKA (pH ≥7.3, bicarbonate ≥15 mEq/L, beta-hydroxybutyrate <1 mmol/L). Secondary outcomes were the rate of fall in blood glucose until 250 mg/dL or less and the rate of complications (hypokalemia, hypoglycemia, and cerebral edema). Sixty patients were analyzed on an intention-to-treat basis (Low-dose group: n=30; Standard-dose group: n=30). Mean (SD) time taken for the resolution of ketoacidosis was similar in both groups [22 (12) vs 23 (18.5) hours; P=0.92]. The adjusted hazard ratio (95% CI) of the resolution of ketoacidosis was lower in the low-dose group [0.40 (0.19 to 0.85); P=0.017]. Mean (SD) rate of blood glucose decrease until 250 mg/dL or less reached [56 (41) vs 64 (65) mg/dL/hour; P=0.41] and time to achieve the target [4.2 (3.1) vs 4.8 (3.3) hours; P=0.44] were similar in both groups. Hypokalemia [30% vs 43.3%; P=0.28] and hypoglycemia [3.3% vs 13.3%; P=0.35] were lower in low-dose group. No child had cerebral edema, and no mortality occurred. Time for resolution of ketoacidosis was similar in the low-dose and standard-dose insulin with a lower rate of therapy-related complications in the low-dose group. Hence, low-dose insulin infusion can be a safer approach in the management of pediatric DKA.

Effects of Low-Dose Ketamine Infusion on Alleviating the Opioid Burden for Patients Undergoing Myomectomy Surgery.

ObjectiveRecent research has focused on the use of N-methyl-D-aspartate (NMDA) receptor antagonists for pain management. Several drugs are known to have this action, including ketamine, which exerts its main analgesic effect through NMDA receptor antagonism. This study aimed to evaluate the effect of low-dose ketamine infusion on opioid exposure for patients undergoing myomectomy surgery under general anaesthesia.MethodsA total of 70 women were included in this prospective double-blind trial study. The patients included in this study were American Society of Anaesthesiologists physical status I–II, aged between 18 and 50 years and scheduled for laparotomy myomectomy surgery. Patients were randomised to receive either a bolus of 0.2 mg kg−1 of ketamine followed by a continuous infusion of 0.2 mg kg−1 hr−1 during the operation or a placebo of normal saline. Both groups also received morphine as needed for pain relief. The primary outcome was the total amount of morphine used during the intraoperative and postoperative periods. Intraoperative and postoperative mean blood pressure, heart rate and postoperative visual analogue scale for pain were assessed.ResultsTotal mean morphine consumption was significantly lower in the ketamine group than in the control group (26±3.5 mg vs. 34.7±3.3 mg, respectively, p<0.05). However, there were no statistical differences between the groups regarding haemodynamics, postoperative pain score and complications.ConclusionThe use of ketamine in low infusion doses intraoperatively during an elective myomectomy procedure produced an opioid-sparing effect by reducing perioperative morphine consumption without significant side effects.

Interest-activity symptom severity predicts response to ketamine infusion in treatment-resistant depression.

Interest and activity are part of the positive mood domain. Evidence suggests the symptom domain of interest-activity at baseline as a clinical predictor for treatment response to traditional antidepressants. However, whether this domain is related to the response to a single low-dose ketamine infusion remains unclear. Seventy-one patients with treatment-resistant depression were randomized to 3 treatment groups: a single 0.5 or 0.2mg/kg ketamine or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale before infusions and at postinfusion period (at 40min and up to 2weeks). Low (mild) versus medium versus high (severe) interest-activity symptom domain groups were classified on the basis of the cutoff point of ± 0.4 standard deviation. The effect of baseline interest-activity symptoms on outcomes was tested using generalized estimating equation models. The interest-activity symptom domain as a continuous variable (β = 8.413, p = .016) was related to the trajectory of depressive symptoms. Stratified by levels of the interest-activity symptom domain, in the low interest-activity, 0.2mg/kg ketamine infusion (β = 0.013) demonstrated the greatest antidepressant effect (p < .01) compared with 0.5mg/kg ketamine (β = 0.739) and placebo infusions; however, in the high interest-activity, 0.5mg/kg ketamine infusion (β = 0.001) demonstrated the best antidepressant effect (p < .01) compared with 0.2mg/kg ketamine (β = 1.372) and placebo infusions. The symptom domain of interest-activity was an independent predictor for the treatment response to a single low-dose ketamine infusion.

Low-Dose Ketamine Infusion as Adjuvant Therapy during an Acute Pain Crisis in Pediatric Patients

Recent studies in pediatric patients have suggested that ketamine, an N-methyl-D-aspartate receptor (NMDA) antagonist, given at sub-anesthetic doses can effectively decrease pain scores, provide analgesic effects, and in some cases, reduce opioid requirements. Our study aims to assess impact of low-dose ketamine on reducing pain scores and total opioid requirements during an acute pain crisis in pediatric patients. From November 2016 to December 2018, eight patients between the ages of 2 and 17 years admitted to the pediatric intensive care unit (PICU) were treated with LDK infusions to manage severe, opioid-refractory, acute pain crises. Subjective pain scores and total morphine milligram equivalent (MME) intake before, during, and after ketamine infusion were collected through a structured chart review. Overall, the addition of ketamine appeared to reduce subjective pain scores and opioid requirements. Two patients were in palliative care and expired shortly after ketamine was started and two patients were discharged within 48 hours of LDK infusion cessation. Ketamine seemed to reduce heart rate and had no appreciable effect on respiratory rate, blood pressure, or oxygen saturation. Hallucination was reported in one patient which resolved upon dose reduction. LDK infusion could be considered as an adjuvant therapy to optimize pain control in pediatric patients experiencing acute pain crises. Further investigation with a larger patient population is warranted to establish the effects of LDK on pain improvement and reducing total opioid requirements.

Efficacy of Low-Dose Epinephrine Continuous Infusion in Neonatal Intensive Care Unit Patients.

Although epinephrine is used in the neonatal intensive care unit, few data exist on efficacy of doses <0.05 mcg/kg/min. This study evaluates the efficacy and safety of low-dose epinephrine continuous infusion at doses <0.05 mcg/kg/min in infants. Single-center, retrospective review of hypotensive infants from 2011-2018. Charts were reviewed for initial and maximum epinephrine doses, additional vasoactive agents, short-term efficacy, and adverse effects. The primary outcome was percentage of patients initiated on low-dose epinephrine whose dose did not require titration to ≥0.05 mcg/kg/min. A total of 115 patients met study criteria with 131 distinct occurrences of low-dose epinephrine initiation. Most patients were unresponsive to other vasopressors at the time of epinephrine initiation. The median (IQR) starting dose of low-dose epinephrine was 0.01 (0.01-0.04) mcg/kg/min and median (IQR) maximum dose was 0.04 (0.02-0.08) mcg/kg/min. Fifty-five percent were responders. Patients in this cohort demonstrated significant improvement of blood pressure and urine output (p < 0.001) without adverse effects. Low-dose epinephrine infusion may be considered as an alternative treatment to standard starting doses in hypotensive neonatal intensive care unit patients.

Postoperative Low-Dose Tranexamic Acid After Major Spine Surgery: A Matched Cohort Analysis.

ObjectiveThis was a retrospective, cohort study investigating the efficacy and safety of continuous low-dose postoperative tranexamic acid (PTXA) on drain output and transfusion requirements following adult spinal deformity surgery. MethodsOne hundred forty-seven patients undergoing posterior instrumented thoracolumbar fusion of ≥ 3 vertebral levels at a single institution who received low-dose PTXA infusion (0.5–1 mg/kg/hr) for 24 hours were compared to 292 control patients who did not receive PTXA. The cohorts were propensity matched based on age, sex, American Society of Anesthesiologist physical status classification, body mass index, number of surgical levels, revision surgery, operative duration, and total intraoperative TXA dose (n = 106 in each group). Primary outcome was 72-hour postoperative drain output. Secondary outcomes were number of allogeneic blood transfusions. ResultsThere was no significant difference in postoperative drain output in the PTXA group compared to control (660 ±420 mL vs. 710 ±490 mL, p = 0.46). The PTXA group received significantly more crystalloid (6,100 ±3,100 mL vs. 4,600 ±2,400 mL, p < 0.001) and red blood cell transfusions postoperatively (median [interquartile range]: 1 [0–2] units vs. 0 [0–1] units; incidence rate ratio [95% confidence interval], 1.6 [1.2–2.2]; p = 0.001). Rates of adverse events were comparable between groups. ConclusionContinuous low-dose PTXA infusion was not associated with reduced drain output after spinal deformity surgery. No difference in thromboembolic incidence was observed. A prospective dose escalation study is warranted to investigate the efficacy of higher dose PTXA.

Beyin Ölümü Tanısı Alan Hastaların Retrospektif Analizi

Amaç: Bu çalışmada beyin ölümü tanılı hastaların özellikleri, organ bağışı oranları ve uygulanan donör bakımının irdelenmesi amaçlanmıştır. Materyal ve Metot: 2013-2020 yılları arasında hastanemizde beyin ölümü tanısı alan hastaların dosyaları taranarak yaş, cinsiyet, yandaş hastalıkları, yatış tanısı, yatış zamanı, beyin ölümü zamanı, tanı testi yöntemleri, organ bağış oranı, nakledilen organların sayıları, donör bakımında uygulanan tedaviler ve kardiyak arrest süresi gibi veriler kaydedildi. Bulgular: Çalışmamızda 41 hastada beyin ölümü tanısı konulurken 6 (%14,6) hastada organ bağışına onay saptandı. Beyin ölümüne en sık yol açan nedenler travmatik beyin hasarı (n=17) ve serebrovasküler olay (n=17) idi. Hastaların yaş ortalamaları 46,73 ± 23,5 (6-80) iken bunların 6’sı çocuk, 21’i yetişkin ve 14’ü yaşlı hasta idi. Hastaların 12’si (%29,3) kadın, 29’u (%70,7) erkekti. Organ bağışı izni verilmeyen 35 hastada ortalama kardiyak arrest süresi 47,17 ± 38,8 (1-167) saat saptandı. Donör bakımında düşük doz dopamin infüzyonu (4 µg/kg/dk), metilprednizolon infüzyonu ve levotiroksin uygulandığı saptandı. Sonuç: Kadavradan organ transplantasyonu için beyin ölümü tanısının konulması önem arz etmektedir. Nörolojik prognozu kötü hastalar beyin ölümü ve potansiyel donör olmaları açısından yakın takip edilmelidir. Organ bağışını arttırmak için eğitimli ve deneyimli organ nakil koordinatörlerine ihtiyaç vardır. Nakledilen organların sayısını ve kalitesini arttırmak için güncel literatüre uygun donör bakımı protokolleri oluşturulmalıdır.

Treatment response to low-dose ketamine infusion for treatment-resistant depression: A gene-based genome-wide association study

BackgroundsEvidence suggested the crucial roles of brain-derived neurotrophic factor (BDNF) and glutamate system functioning in the antidepressant mechanisms of low-dose ketamine infusion in treatment-resistant depression (TRD). Methods65 patients with TRD were genotyped for 684,616 single nucleotide polymorphisms (SNPs). Twelve ketamine-related genes were selected for the gene-based genome-wide association study on the antidepressant effect of ketamine infusion and the resulting serum ketamine and norketamine levels. ResultsSpecific SNPs and whole genes involved in BDNF–TrkB signaling (i.e., rs2049048 in BDNF and rs10217777 in NTRK2) and the glutamatergic and GABAergic systems (i.e., rs16966731 in GRIN2A) were associated with the rapid (within 240 min) and persistent (up to 2 weeks) antidepressant effect of low-dose ketamine infusion and with serum ketamine and norketamine levels. DiscussionOur findings confirmed the predictive roles of BDNF–TrkB signaling and glutamatergic and GABAergic systems in the underlying mechanisms of low-dose ketamine infusion for TRD treatment.

Propofol plus low-dose dexmedetomidine infusion and postoperative delirium in older patients undergoing cardiac surgery

BackgroundPostoperative delirium (POD) is a frequent complication in older patients. Dexmedetomidine might be effective in decreasing the incidence of POD. We hypothesised that adding low-dose rate dexmedetomidine infusion to a propofol sedation regimen would have fewer side-effects and would counteract the possible delirium producing properties of propofol, resulting in a lower risk of POD than propofol with placebo. MethodsIn this double-blind placebo-controlled trial, patients ≥60 yr old undergoing on-pump cardiac surgery were randomised 1:1 to the following postoperative sedative regimens: a propofol infusion and dexmedetomidine (0.4 μg kg−1 h−1) or a propofol infusion and saline 0.9% (placebo group). The study drug was started at chest closure and continued for 10 h. The primary endpoint was in-hospital POD, assessed using the Confusion Assessment Method and chart review method. ResultsPOD over the course of hospital stay occurred in 31/177 (18%) and 33/172 (19%) patients in the dexmedetomidine and placebo arm, respectively (P=0.687; odds ratio=0.89; 95% confidence interval, 0.52–1.54). The incidence of POD in the intensive care alone, or on the ward alone, was also not significantly different between the groups. Subjects in the dexmedetomidine group spent less median time in a delirious state (P=0.026). Median administered postoperative norepinephrine was significantly higher in the dexmedetomidine group (P<0.001). One patient in the dexmedetomidine group and 10 patients in the placebo group died in the hospital. ConclusionsAdding low-dose rate dexmedetomidine to a sedative regimen based on propofol did not result in a different risk of in-hospital delirium in older patients undergoing cardiac surgery. With a suggestion of both harm and benefit in secondary outcomes, supplementing postoperative propofol with dexmedetomidine cannot be recommended based on this study. Clinical trial registrationNCT03388541.

Low-Dose Ketamine Infusion Versus Morphine Infusion During Abdominoplasty to Change the Postoperative Pain Profile.

BackgroundWith the increased number of abdominoplasty all over the world, and the need to manage postoperative pain, it is a must to find proper and effective drugs to decrease opioid consumption in the postoperative period.ObjectivesIn this double-blind randomized controlled clinical trial, we assumed that low-dose ketamine infusion will reduce the postoperative pain profile than the conventional method of morphine.MethodsThe scheduled patients for abdominoplasty under general anesthesia were recruited in two groups: group (K) with low-dose ketamine infusion intra-operatively (80 patients) and group (M) with morphine infusion intra-operatively (80 patients). Both groups were monitored intraoperatively and postoperatively for rescue doses of fentanyl, visual analogue scale (VAS), and side effects.ResultsThere were no statistical differences between both groups regarding the fentanyl rescue doses intra- and postoperative with no remarkable side effects.ConclusionsLow-dose ketamine has a useful analgesic effect in abdominoplasty similar to morphine without remarkable side effects, such as sedation or hallucinations.

701: Adjunct Low-Dose Ketamine Infusion in Critically Ill Patients at a Saudi Hospital (ATTAINMENT Trial)

INTRODUCTION: A noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care (SOC) in critically ill patients on mechanical ventilation (MV) for ≥ 24 h METHODS: This trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult intensive care unit (ICU) patients (> 14 years old) on MV at King Faisal Specialist Hospital and Research Center, Saudi Arabia, and will enroll 80 patients Patients was randomized post-intubation into two groups: the intervention group received an adjunct lowdose ketamine infusion plus SOC administered over a period of 48 h at a fixed infusion rate of 2 μg/kg/min (0 12 mg/kg/h) in day 1 followed by 1 μg/kg/min (0 06 mg/kg/h) in day 2 The control group received SOC (propofol and/or fentanyl and/or midazolam) according to our sedation and analgesia protocol as clinically appropriate The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first RESULTS: As of 25 July 2020, a total of 65 patients had been enrolled We expect to complete the recruitment by 31 December 2020 Recruitment rate has been slowed down due to COVID-19 pandemic An Interim analysis was conducted and showed 45% were in medical ICU, 35 % in surgical ICU, and 20 % in transplant/oncology ICU, range SOFA 2-18, and APACHE II 7-39 About 70 % of the patients was extubated within 28 days post-randomization to ketamine compared to 50 % randomized to SOC The percentage of the patient at goal RASS in 48 hours is 61 11 % in ketamine vs 57 89 % in SOC No significant difference between the 2 arms in 28 days mortality CONCLUSIONS: The findings of this pilot trial will justify further investigation for the role of adjunct low-dose ketamine infusion as an analgo-sedative agent in a larger, multicenter, randomized controlled trial The trial is registered at ClinicalTrials gov: NCT04075006, Saudi Food and Drug Authority: SCTR #19063002, and Current controlled trials: ISRCTN14730035

Perioperative Intravenous Low-Dose Ketamine Infusion to Minimize Pain for Septorhinoplasty: A Prospective, Randomized, Double-Blind Study.

Studies investigating the effects of intravenous (IV) ketamine in pain management after septorhinoplasty is limited. This study aims to evaluate the efficacy of low-dose IV infusion of ketamine on pain scores. This randomized, prospective, double-blind study was conducted with 48 patients who underwent septorhinoplasty. Intravenous ketamine bolus (0.5 mg/kg) was administered to the ketamine group (group K, n = 24) at anesthesia induction, and ketamine infusion was continued (0.25 mg/kg/h) during the surgery. In the control group (group C, n = 24), the same protocol was administered using saline instead of ketamine. Furthermore, 50-mg dexketoprofen trometamol was administered to both groups 30 minutes before the end of the surgery. Then it was repeated at the 12th and 24th hours postoperatively. Pain scores were evaluated with the visual analogue scale. Consumptions intraoperative of opioid and sevoflurane, rescue opioid requirement, patient satisfaction, and side effects were recorded. Pain scores were significantly lower in group K at all postoperative periods (P < .05). There was no significant difference between the groups in terms of intraoperative sevoflurane and remifentanil consumptions (P > .05). Rescue opioid analgesic requirements were significantly lower in group K than group C (0/24 vs 6/24, respectively; P = .022). Side effects were similar between the groups (P > .05). We recommend the administration of low-dose ketamine infusion during septorhinoplasty surgery because it reduces the requirement for rescue opioid analgesia and postoperative pain scores.