Low-dose Infusion Research Articles

A randomised comparative study of erector spinae plane block versus low-dose ketamine-dexmedetomidine intravenous infusion as intraoperative opioid-free analgesia for modified radical mastectomy.

Opioid-sparing analgesia for acute postoperative pain after breast cancer surgery is crucial due to opioid-related side effects. The utilisation of erector spinae plane block and low-dose intravenous ketamine-dexmedetomidine are widely recognised as non-opioid analgesic methodologies. The objective of this study was to conduct a randomised trial to examine the analgesic efficacy of both approaches while minimising the use of opioids. Seventy-two female patients scheduled for unilateral modified radical mastectomy were recruited. They were allocated randomly to Group ESPB, which received ipsilateral ultrasound-guided erector spinae plane block by 20 mL bupivacaine 0.5% at the level of T5 after induction of general anaesthesia, and Group Ket-Dex, which received intravenous (IV) bolus 0.25 mg/kg of ketamine and 0.5 µg/kg of dexmedetomidine, followed by an IV infusion of 0.25 mg/kg of ketamine and 0.3 µg/kg of dexmedetomidine per hour. Total postoperative morphine consumption (24 h) was the primary outcome. The secondary outcomes were pain scores over 24 hours during rest, duration of analgesia, isoflurane consumption, time to awakening, postoperative nausea and vomiting (PONV), and postoperative serum cortisol level. The postoperative morphine consumption over 24-hour in Group ESPB was 3.26 mg (0-6.74) versus 2.35 mg (2.08-4.88) in Group Ket-Dex (P = 0.046). Group Ket-Dex had lower pain scores at rest, longer analgesia duration, longer awakening time, and lower postoperative serum cortisol levels. Intravenous low-dose ketamine-dexmedetomidine infusion intraoperatively with inhalational-based general anaesthesia provides superior opioid-sparing analgesia to that of ESPB in patients undergoing unilateral non-reconstructive modified radical mastectomy, with less postoperative opioid consumption and stress response.

A study of a new mechanism: Intracellular retention allo-CART safety and efficacy for extranodal bulky B-NHL.

e19007 Background: Extranodal bulky lesions, a significant adverse prognostic factor in lymphoma, commonly denote a more aggressive disease course, mandating prompt and intensified treatment strategies. In response, we developed ThisCART19A, a non-genetic editing and off-the-shelf anti-CD19 CAR T-cell therapy incorporating intracellular retention of membrane proteins, representing a novel approach that downregulates surface expression of TCRαβ/CD3 complexes. ThisCART19 has exhibited a favorable safety profile and promising efficacy in patients with relapsed/refractory bulky B-cell Non-Hodgkin Lymphoma. Methods: This is an investigator-initiated trial employing an open-label, dose escalation, and expansion design to evaluate the safety and efficacy of ThisCART19A in patients with relapsed or refractory bulky B-cell non-Hodgkin lymphoma (B-NHL). Bulky disease was defined as the longest diameter of the mass >5 cm at baseline. Results: Between June, 2021, and June, 2023, 13 extranodal bulky disease were enrolled in the studies and successfully received ThisCART19A. The median age was 56 (range, 37~67) years. All 13 patients had 3 median prior lines of therapy (range, 2-5). All patients received anti-CD20 and multi- agent chemotherapy. 8 (61.54%) patients had prior auto CART. mSPD was 48 (range, 16~162) cm². mTMTV was 114.9 (range, 14~483) ml. As of February 2024, The most common adverse events were CRS (100%) , infections (30.77%), ICANS (23.08%) and cytopenias(100%); This is no grade 3 or higher CRS occurred;only 1(7.69%)patient experienced grade 4 ICANS and relieved after intravenous dexamethasone treatment. This is no treatment-related deaths occurred. Among the 13 patients, 10 were evaluable, with an ORR and CR of 90% and 80%, respectively, at 28 days post-infusion. mPFS was 62 days (range, 28~227). The patient who achieved a PR received chemotherapy and radiotherapy as consolidation, As of February 5th, 2024, the patient has survived for 263 days and is still under follow-up. Additionally, two patients progressed after CR received sequential chemotherapy and BCL-2 Inhibitor, with an average OS of 326.5 days, still being under follow-up. In 13 evaluable patients, the mean C-max was 1043.13 cells/μL(range, 0.59~10045.4), and the mean AUC0-28d was 1542.23 cells/μL × day(range, 0.91~11724).In this cohort, two patients received low-dose infusions at 1×106 cells/kg and still achieved excellent expansion, the respective C-max were 726.432 cells/μL and 336.67 cells/μL. Conclusions: This CART19A exhibited favorable safety, remarkable expansion potential, and efficacy profiles in the treatment of r/r bulky lymphoma. Notably, it achieved a high ORR of 90%, providing a favorable window of opportunity for subsequent consolidation and intensification treatments. Moreover, this transition from a bulky to a non-bulky disease state reduces the intricacy of follow-up treatments. Clinical trial information: NCT04384393 .

Management and treatment of perioperative hypersensitivity.

Perioperative hypersensitivity reactions are rare but potentially catastrophic events. This review acts to summarize recent recommendations for both immediate and poststabilization management of suspected reactions, alongside practical advice for anaesthetists who may be faced with these events. Prompt treatment is essential but may be hampered by delay in recognition. This can occur because there are multiple differential diagnoses for the observed clinical signs as well as variations in clinical presentation. Resuscitation is dependent on the use of adrenaline and fluids. Adrenaline should be administered in small, titrated intravenous boluses. Low-dose infusions should be commenced early if the response to boluses is poor. Large volume fluid resuscitation may be required to maintain adequate circulating volume. Chest compressions are recommended when there is evidence of inadequate perfusion, rather than waiting until cardiac arrest is confirmed. Antihistamines and corticosteroids are no longer recommended in the immediate management phase. Once the patient has been stabilized, it is important to obtain serial tryptase concentrations to aid the subsequent clinic investigation. The decision to proceed or abandon surgery will be based on an individual risk-benefit analysis. All cases of suspected perioperative hypersensitivity, including fatal cases, must be referred for formal investigation. There have been recent updates to management guidelines in perioperative hypersensitivity. Treatment algorithms, treatment packs and referral packs can all help the anaesthetist manage these complex cases, aid the subsequent investigation and ensure patient safety in the future.

Low-dose short infusion ketamine as adjunct to morphine for acute long bone fracture in the emergency department: a randomized controlled trial

BackgroundKetamine is recognized as an alternative for pain management; however, concerns about emergent adverse reactions have limited its widespread adoption. This study aimed to assess the efficacy of a short infusion of low-dose ketamine (LDK) compared to intravenous morphine (MOR) as adjunctive analgesia for acute long bone fracture pain.MethodsThis single-blinded, randomized controlled trial was conducted in a single emergency department. Patients with acute long bone fractures and numerical rating scale (NRS) pain scores ≥ 6 following an initial dose of intravenous morphine were assigned to receive either a LDK (0.3 mg/kg) over 15 min or intravenous MOR at a dose of 0.1 mg/kg administered over 5 min. Throughout a 120-min observation period, patients were regularly evaluated for pain level (0–10), side effects, and the need for additional rescue analgesia.ResultsA total of 58 subjects participated, with 27 in the MOR group and 31 in the LDK group. Demographic variables and baseline NRS scores were comparable between the MOR (8.3 ± 1.3) and LDK (8.9 ± 1.2) groups. At 30 min, the LDK group showed a significantly greater mean reduction in NRS scores (3.1 ± 2.03) compared to the MOR group (1.8 ± 1.59) (p = 0.009). Similarly, at 60 min, there were significant differences in mean NRS score reductions (LDK 3.5 ± 2.17; MOR mean reduction = 2.4, ± 1.84) with a p-value of 0.04. No significant differences were observed at other time intervals. The incidence of dizziness was higher in the LDK group at 19.4% (p = 0.026).ConclusionShort infusion low-dose ketamine, as an adjunct to morphine, is effective in reducing pain during the initial 30 to 60 min and demonstrated comparability to intravenous morphine alone in reducing pain over the subsequent 60 min for acute long bone fractures. However, it was associated with a higher incidence of dizziness.Trial registrationNMRR17318438970 (2 May 2018;www.nmrr.gov.my).

Combined low-dose dobutamine and exercise stress echocardiography: a new hybrid protocol to detect inducible ischaemia.

Myocardial response to stress echocardiography may be elicited physiologically, through exercise, or pharmacologically, often with dobutamine. Both have advantages but also limitations due to reduced exercise capacity or side-effects to stressor agent/lack of closeness to true pathophysiology of ischaemic cascade. We have combined low-dose dobutamine and exercise, creating a 'hybrid' protocol to utilize the advantages of both techniques and limit the drawbacks. The aim of the study was to evaluate its safety and feasibility. In the hybrid protocol, low-dose dobutamine infusion (up to 10 µg/kg/min) is enhanced by supine bicycle exercise at 3-min increments of workload of 25 W to achieve target heart rate (THR). We analysed safety and outcome data for all the patients who underwent this protocol from 2017 to 2022. Out of 835, 727 (87.1%) patients referred for evaluation of ischaemia underwent the hybrid protocol. The median age was 61 years old and 61% (442/727) were men. The median exercise time was 11 (9-13.5) min with a median maximum workload of 100 W (75-125). Out of 727, 670 (92.2%) achieved THR. Atropine was not used. Out of 727, 192 (26.4%) of studies were positive for ischaemia. Out of 122, 102 (83.6%) with positive stress who underwent invasive angiography had significant coronary disease. The incidence of complications was low: 1/727-severe arrhythmia, 5/727 (0.7%) developed a vasovagal episode, and 14/727 (1.9%) had a hypertensive response to exercise. Our findings suggest that this protocol is safe, feasible, and has a high success rate in achieving THR.

Implementation of perioperative blood glucose monitoring and insulin infusion protocol can decrease postoperative infection rate in diabetic patients undergoing elective craniotomy: An observational study

BackgroundSevere perioperative hyperglycemia (SH) is a proven risk factor for postoperative complications after craniotomy. To reduce this risk, it has been proposed to implement the standardized clinical protocol for scheduled perioperative blood glucose concentration (BGC) monitoring. This would be followed by intravenous (IV) insulin infusion to keep BGC below 180 mg/dl in the perioperative period. The aim of this prospective observational study was to assess the impact of this type of protocol on the postoperative infection rate in patients undergoing elective craniotomy. MethodsA total of 42 patients were prospectively enrolled in the study. Protocol included scheduled BGC monitoring in the perioperative period and rapid-acting insulin IV infusion when intraoperative SH was detected. The diagnosis of infection (wound, pulmonary, blood stream, urinary tract infection or central nervous system infection) was established according to CDC criteria within the first postoperative week. A previously enrolled group of patients with sporadic BGC monitoring and subcutaneous insulin injections for SH management was used as a control group. ResultsAn infectious complication (i.e., pneumonia) was diagnosed only in one patient (2 %) in the prospective group. In comparison with the control group, a decrease in the risk of postoperative infection was statistically significant with OR = 0.08 [0.009 – 0.72] (p = 0.02). Implementation of the perioperative BGC monitoring and the correction protocol prevented both severe hyperglycemia and hypoglycemia with BGC < 70 mg/dl. ConclusionScheduled BGC monitoring and the use of low-dose insulin infusion protocol can decrease the postoperative infection rate in patients undergoing elective craniotomy. Future studies are needed to prove the causality of the implementation of such a protocol with an improved outcome.

Cardioprotective Effects of Sodium-Glucose Cotransporter Subtype Inhibition on Ischemic and Pharmacological Preconditioning.

Sodium-glucose cotransporter (SGLT) 2 inhibitors partially inhibit SGLT1 expression; however, whether a clinical dose of SGLT2 inhibitor abrogates ischemic preconditioning (IPC) is unknown, and the pharmacological cardioprotective effect under SGLT1 inhibition has not been examined. In this study, we investigated whether a clinical dose of tofogliflozin abrogates IPC and whether pharmacological preconditioning with olprinone has cardioprotective effects under SGLT1 inhibition. Male Wistar rats were divided into seven groups (seven rats per group) and subjected to the following treatments before inducing ischemia/reperfusion (I/R; 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion): saline infusion control treatment (Con); ischemic preconditioning(IPC); IPC after phlorizin infusion (IPC+Phl); IPC after low-dose tofogliflozin infusion (IPC+L-Tof); IPC after high-dose tofogliflozin infusion (IPC+H-Tof); olprinone infusion (Olp); and Olp infusion after phlorizin infusion (Olp+Phl). The infarct size was significantly decreased in the IPC group, but not in the IPC+Phl group. In contrast, the infarct size decreased in the IPC+L-Tof and IPC+H-Tof groups. Additionally, Olp reduced the infarct size, and the effect was preserved in Olp+Phl groups. Phosphorylated AMP-activated protein kinase (AMPK) expression was lower in the IPC+Phl group compared to that in the IPC group. The cardioprotective effect of IPC was attenuated by strong SGLT1 inhibition, but the effect was preserved under a clinical dose of highly selective SGLT2 inhibitor. Olprinone exerts a cardioprotective effect even under strong SGLT1 inhibition.

Gut bacteria contribute to rodent hypertension via modulation of colonic serotonin and gut vagal 5ht3aRs

Hypertension is associated with gut dysbiosis and autonomic dysfunction in humans and rodent models. While hypertension-associated gut dysbiosis elevates blood pressure in rodents, the precise mechanisms are unknown. In our model gut dysbiosis-induced hypertension, fecal matter transplant from hypertensive SHR reduced colonic serotonin and relative expression of serotonergic 5ht3a receptors (5ht3aRs) on vagal afferents in the control WKY rats. To investigate the role of serotonergic gut vagal axis in regulation of blood pressure, in a cre-dependent manner we first overexpressed channelrhodopsin 2 in the 5ht3aR-expressing gut-projecting vagal afferents (NG5ht3Ar) in 5ht3aR Cre rats. Acute bilateral optic stimulation of NG5ht3Ar produced an immediate decrease in blood pressure and heart rate. Conversely, chronic ablation of NG5ht3Ar by cre-dependent expression of caspase elevated blood pressure in 5ht3aR Cre rats. This effect was potentiated both by the infusion of low dose of angiotensin II and exposure to acute restraint stress separately. On the other hand, overexpression of 5ht3aRs in NG5ht3Ar reduced blood pressure in the SHR, the effect that was further potentiated by dietary tryptophan supplementation. Altogether, these data propose that hypertension-associated microbiota contribute to rodent hypertension via modulation of colonic serotonin and gut vagal 5ht3aRs. NIHR01HL152162. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Low-dose Ketamine Infusion on Opioid Consumption in Children Undergoing Open Cardiac Surgery: A Randomized Controlled Double-Blind Study

This study was designed to evaluate the effect of low-dose ketamine infusion on the perioperative consumption of opioids in pediatric open cardiac surgery. A randomized, controlled, double-blinded single-center study was conducted. The study took place in a tertiary care children's hospital. Patients of both sexes aged 2-12 years who underwent cardiac surgery were included. Patients in the ketamine group received a bolus of 0.3 mg/kg of ketamine before skin incision followed by continuous intraoperative infusion of 0.25 mg/kg/h and postoperative infusion of 0.1 mg/kg/h for 24 h. Patients in the control groups received volumes of normal saline either bolus or continuous infusion like that of the ketamine group. The primary outcome was the total dose of fentanyl consumed over the first 24 hours postoperatively. Secondary outcomes were intraoperative fentanyl consumption, time to extubation, modified objective pain score, and incidence of vomiting, pruritus, diplopia, or hallucinations. A total of 80 patients were recruited but the final analysis was done on 35 patients in the ketamine group and 34 in the control group. Fentanyl consumption during surgery and in the first 24 hours postoperatively was significantly lower in the ketamine than the control group. Patients in both the ketamine and control groups had similar times to extubation. Modified objective pain scores were significantly lower in the ketamine group than the control group. None of the patients in either group had diplopia or hallucinations. Low-dose ketamine infusion in children undergoing open cardiac surgery reduced intra- and postoperative opioid consumption and postoperative pain scores. Moreover, ketamine did not cause diplopia or hallucinations.

Effectiveness of Intravenous Low-Dose Ketamine Versus Morphine for Procedural Burn Pain Management During Dressing Changes: A Randomized Clinical Trial

Background: There is limited literature on using low-dose intravenous ketamine as a single agent for procedural burn pain management during adult dressing changes. Aims &amp; Objectives: To determine the effectiveness of low-dose ketamine compared to morphine as a single analgesic agent in procedural burn pain management during dressing changes. Materials &amp; Methods: We performed an institutional review board-approved, randomized, prospective, double-blinded, controlled, non-inferiority trial. All adult patients 18 years and above scheduled for dressing change were screened. Patients who consented were randomized to receive low-dose ketamine infusion at 0.2mg/kg/hr. In the treatment group, morphine infusion at 0.1mg/kg/hr. In the control group. The primary endpoint was pain intensity, measured using a visual analog scale. Data were analyzed on an intention-to-treat (ITT) approach. Secondary endpoints included rescue analgesia requirements and the occurrence of adverse effects in both groups. Results: 82 patients were enrolled (ketamine 41 vs. morphine 41). We compared VAS scores at 5-minute intervals during the dressing changes. Overall, pain scores are similar in both groups (p-value=0.595). The pain control was homogenous. However, the morphine group required more rescue analgesia throughout the dressing changes than the low-dose ketamine group (p=0.013 at T15, p&lt;0.001 at T20, and p&lt;0.001 at T30). The occurrence of side effects was similar in both groups. Conclusion: This study suggests that low-dose ketamine provides as effective and more predictable procedural analgesia as morphine during dressing procedures for adult burn patients.

Efficacy of Low-Dose Streptokinase Infusion in Late-Onset Permanent Tunnel Catheter Dysfunction: A Single-Center Interventional Study.

Introduction Hemodialysis is a vital modality for patients with renal dysfunction, with venous access being a significant factor in its success. While arteriovenous fistulas are preferred, tunneled catheters serve as important alternatives, especially in challenging cases. Late-onset tunneled catheter dysfunction, often due to fibrin sheath formation, impedes hemodialysis efficiency. Streptokinase, a low-cost thrombolytic agent, has shown promise in resolving such complications, yet its efficacy in the Indian context remains unexplored. Methods We conducted a single-center interventional study at Mahatma Gandhi Mission (MGM) Hospital, Aurangabad, India, from May 2023 to October 2023. Ethical approval was obtained, and 10 eligible patients experiencing late-onset permanent tunnel catheter dysfunction were enrolled. Patients were treated with low-dose streptokinase, and outcomes were monitored for 60 days. Results Ten patients, evenly distributed by gender, participated, with a mean age of 48.2 ± 11.96 years. Diabetes was the predominant cause of chronic kidney disease (CKD) at 33% (3/10). All patients achieved the primary endpoint of blood flow rate (BFR) >300 ml/min post-streptokinase treatment, with an overall success rate of 100%. Group A had the highest average gain in catheter days (80.6 ± 7.59), followed by Group B (64 ± 1), while Group C showed variations in catheter days between the first (26.2 ± 6.8) and second insertion (32.5 ± 1.76). Eight patients maintained catheter patency during the 60-day follow-up. Adverse effects, primarily minor, were observed. The dosage rationale involved an eight-hour infusion at 4,000 units per hour. Conclusion Streptokinase emerges as cost-effective and efficacious for maintaining the patency of late-onset tunnel catheter dysfunction in resource-limited settings, particularly in younger patients. Caution is advised for older individuals with prolonged CKD.

Concurrent chemoradiation with low-dose and long-duration weekly infusion of gemcitabine in unresectable squamous cell carcinoma of head and neck (SCCHN).

Concurrent chemoradiotherapy now represents the standard of care in locally advanced unresectable squamous cell carcinoma of the head and neck, and the administration of cisplatin in triweekly or weekly schedules is the most commonly used chemotherapeutic agent. However, the chemotherapeutic agent and its scheduling with radiation is still an area of investigation with safer toxicity profile and better response rates. Gemcitabine is a potent radiosensitizer, and non-cytotoxic concentration results in decreased systemic toxicity while maintaining radiosensitization properties. Furthermore, data are emerging for low-dose and long-duration infusion where this strategy is found to be effective and a safe alternative to standard brief infusion. Based on these two strategies, that is, non-cytotoxic concentration with long duration, we have explored the unique possibility of further lowering the toxicity profile without compromising the efficacy. Eligible patients of locally advanced unresectable squamous cell carcinoma of the head and neck underwent radiation treatment with concurrent gemcitabine. A total dose of 70 Gy in 35 fractions over a period of seven weeks with conventional fractionation schedule was delivered with cord off after 44 Gy. Concurrent gemcitabine was administered intravenously for over two hours once a week, 1-2 h before radiation and for seven consecutive weeks at 50 mg/m2. Fifty-two patients was enrolled in this study, out of which 41 completed the treatment. Fifty-nine percent completed treatment within seven weeks. Sixty-four percent were found to have received more than five cycles. Mean follow-up of patients was found to be 4.9 months. Sixty-eight percent had complete response. Stage III patients achieved more complete response compared to stage IV. There was no site-wise difference in achieving complete response. Patients who have received less than five chemo cycles or completed the treatment in more than seven weeks had less complete response. Sixty-one percent had severe mucositis while 39% developed mild/moderate mucositis. Considering skin toxicity, 80% were found to have mild/moderate skin toxicity, while only 20% suffered from severe grades of skin toxicity. Gemcitabine in low-dose and long-duration infusion is a potent radiosensitizer with safer hematological toxicity and manageable local toxicities.

Predictors of low-dose ketamine infusion to optimize pain management in the post-anesthesia care unit (PACU)

Predictors of low-dose ketamine infusion to optimize pain management in the post-anesthesia care unit (PACU)

Low-dose ketamine infusion to facilitate opioid tapering in chronic non-cancer pain with opioid-use disorder: a historical cohort study

BackgroundLong-term opioid use is associated with pharmacological tolerance, a risk of misuse and hyperalgesia in patients with chronic pain (CP). Tapering is challenging in this context, particularly with comorbid opioid-use...

Preclinical assessments of safety and tumorigenicity of very high doses of allogeneic human umbilical cord mesenchymal stem cells

Human umbilical cord-mesenchymal stem cells (hUC-MSCs) have been widely investigated as a new therapeutic agent to treat injuries and inflammatory-mediated and autoimmune diseases. Previous studies have reported on the safety of low-dose infusion of hUC-MSCs, but information on the cell behaviour at higher doses and frequency of injection of the cells remains uncertain. The aim of the present study was to demonstrate the safety and efficacy of hUC-MSCs by Cytopeutics® (Selangor, Malaysia) from low to an extremely high dose in different monitoring periods in healthy BALB/c mice as well as assessing the tumorigenicity of the cells in B-NDG SCID immunocompromised mice. Umbilical cord from two healthy human newborns was obtained and the isolation of the hUC-MSCs was performed based on previous established method. Assessment of the cells at different doses of single or multiple administrations was performed on healthy BALB/c mice in dose range finding, sub-acute (7 d and 28 d) and sub-chronic periods (90 d). Tumorigenicity potential of Cytopeutics® hUC-MSCs was also evaluated on B-NDG immunocompromised mice for 26 wk. Single or multiple administrations of Cytopeutics® hUC-MSCs up to 40 × 106 cells per kilogramme of body weight (kg BW) were found to have no adverse effect in terms of clinical symptoms, haematology and other laboratory parameters, and histology examination in healthy BALB/c mice. hUC-MSCs were also found to reduce pro-inflammatory cytokines (IL-6 and TNF-α) in a dose-dependent manner. No sign of tumor formation was observed in B-NDG mice in the 26-wk tumorigenicity assessment. Single or multiple administration of allogenic Cytopeutics® hUC-MSCs was safe even at very high doses, is non-tumorigenic and did not cause adverse effects in mice throughout the evaluation periods. In addition, Cytopeutics® hUC-MSCs exhibited immunomodulatory effect in a dose-dependent manner.

Effectiveness of perioperative low-dose esketamine infusion for postoperative pain management in pediatric urological surgery: a prospective clinical trial

BackgroundPostoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery.MethodsPediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded.ResultsIn comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021).ConclusionsThe use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients.Trial registrationChinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023).

Respuesta hemodinámica a dosis subanestésicas de ketamina en dolor posoperatorio: revisión sistemática

Introduction: Low-dose ketamine infusions have shown analgesic effectiveness for the management of postoperative pain. The impact of low-dose ketamine infusions on cardiovascular response is dose-dependent and requires a better knowledge about its effects on this population.&#x0D; Objective: To conduct a systematic review to describe changes in systolic, diastolic and mean arterial pressure, and heart rate 24, 48 and 72 hours after surgery.&#x0D; Methods: Randomized, controlled trials were reviewed in the Cochrane Library, PubMed, EMBASE, SciELO, Lilacs and grey literature on low-dose ketamine infusions for the study variables. The quality of the studies was assessed using the Cochrane’s risk of bias tool.&#x0D; Results: Six randomized, controlled trials with 641 patients were included. Low-quality evidence was found suggestive of a lack of certainty of any significant differences in the systolic blood pressure variables at 24 hours (mean standard deviation -1.00, 95 % CI: -7.27 to 5.27). A statistically significant higher mean heart rate at 24 hours was identified in the low-dose ketamine infusion group, (mean standard deviation 1.64 95 % CI: 0.38 to 2.90) which did not reach clinical significance. A lower pain level and less use of opioids was identified in the low-dose ketamine infusion group.&#x0D; Conclusion: Low quality evidence was found, suggesting that low-dose ketamine infusions are not associated with significant changes in blood pressure or heart rate 24 – 48 hours after surgery. It is important to individualize cardiovascular risk for each case, before initiating treatment.

Real-world comparison of low- versus high-dose continuous 5FU infusion in patients receiving triplet chemotherapy plus bevacizumab for newly diagnosed metastatic colorectal cancer (mCRC).

62 Background: Several randomized trials demonstrated an overall survival (OS) benefit to triplet chemotherapy (5-FU, oxaliplatin, and irinotecan) plus bevacizumab compared to doublet chemotherapy plus bevacizumab in patients with newly diagnosed mCRC, though with higher rates of neutropenic fever and diarrhea. These trials used high-dose continuous infusion 5-FU (3,200 mg/m2/48 hours), but national guidelines suggest low-dose continuous infusion 5-FU (2,400mg/m2/48 hours) due to lower tolerance in U.S. patients. We performed a retrospective cohort study in a U.S. population to compare the effectiveness of low- vs high-dose continuous infusion 5FU in patients undergoing triplet chemotherapy plus bevacizumab for newly diagnosed mCRC. Methods: We used the nationwide Flatiron Health electronic health record-derived database, comprising de-identified patient-level structured and unstructured data curated via technology-enabled abstraction from ~280 cancer clinics. Patients with newly diagnosed mCRC who initiated triplet chemotherapy plus bevacizumab between 10/23/14 and 10/31/22 with non-missing height, weight, and dosing data were included. 5FU infusion doses of 2,000 – 2,799 mg/m2 were categorized as low-dose while those &gt;/= 2,800 mg/m2 were categorized as high-dose. OS from first-line treatment initiation was assessed by dosing group using the Kaplan Meier method with log-rank testing. Multivariable analysis with adjustment for pre-specified variables with imbalance (defined by standardized difference &lt; - 0.10 or &gt; 0.10) was performed using multivariable Cox proportional hazards modeling. Missing data were imputed using multiple imputation with chained equations. Results: Among 320 patients included, 244 received low-dose and 76 patients received high-dose continuous infusion 5FU. Imbalance between low- and high-dose groups was observed in the use of 5FU bolus (23% vs 3%), year of metastatic diagnosis 2018 - 2022 (80% vs 55%), mean irinotecan dose (156.4 vs 160.5 mg/m2), left-sided primary (73% vs 64%), MMR deficiency (3% vs 6%) and mean CEA (478 vs 691 µg/L). In univariate analysis, median OS was 33 months (95% CI 26 – 39) in the low-dose group compared to 34 months (95% CI 24 – 48) in the high-dose group (HR 1.16; 95% CI 0.79 – 1.69; p = 0.44). After adjusting for imbalanced covariates, there was no difference in hazard of death between low- and high-dose groups (HR 0.99; 95% CI 0.64 – 1.53; p = 0.97). Conclusions: In this real-world, U.S. population with newly diagnosed mCRC receiving triplet chemotherapy plus bevacizumab, there was no association with survival between low- vs high-dose continuous infusion 5FU. This supports current guidelines recommending low-dose continuous infusion 5FU (2,400mg/m2/48 hours) for patients with mCRC receiving triplet chemotherapy in the U.S.

Prevalence of Delirium After Abdominal Surgery and Association With Ketamine: A Retrospective, Propensity-Matched Cohort Study.

Delirium is a common postoperative complication for older patients in the ICU. Ketamine, used primarily as an analgesic, has been thought to prevent delirium. Determine the prevalence and association of delirium with low-dose ketamine use in ICU patients after abdominal surgery. Single-center, retrospective, propensity-matched cohort study. Eight hospital academic medical center. Cohort comprising 1836 patients admitted to the ICU after abdominal surgery between June 23, 2018 and September 1, 2022. Propensity score matching (PSM) with a 3:1 ratio between no-ketamine use and ketamine use was performed through a greedy algorithm (caliper of 0.005). Outcomes of interest included: delirium (assessed by Confusion Assessment Method-ICU), mean pain score (Numeric Pain Scale or Critical Care Pain Observation Tool score as available), mean opioid consumption (morphine milligram equivalents), length of stay (d), and mortality. Prevalence of delirium was 47.71% (95% CI, 45.41-50.03%) in the cohort. Of 1836 patients, 120 (6.54%) used low-dose ketamine infusion. After PSM, the prevalence of delirium was 56.02% (95% CI, 51.05-60.91%) in all abdominal surgery patients. The ketamine group had 41% less odds of delirium (odds ratio [OR] = 0.59; 95% CI, 0.37-0.94; p = 0.026) than patients with no-ketamine use. Patients with ketamine use had higher mean pain scores (3.57 ± 2.86 vs. 2.21 ± 2.09, p < 0.001). In the subgroup analysis, patients in the ketamine-use group 60 years old or younger had 64% less odds of delirium (OR = 0.36; 95% CI, 0.13-0.95; p = 0.039). The mean pain scores were higher in the ketamine group for patients 60 years old or older. There was no significant difference in mortality and opioid consumption. Low-dose ketamine infusion was associated with lower prevalence of delirium in ICU patients following abdominal surgery. Prospective studies should further evaluate ketamine use and delirium.

Intraoperative low-dose ketamine infusion for postoperative pain relief in laparoscopic surgeries – A randomised, double blind controlled clinical trial

Abstract Background: Patients undergoing laparoscopic surgery often experience moderate-to-severe postoperative pain. The use of opioids for postoperative pain relief often results in respiratory depression and other adverse effects. Hence, we studied the effect of ketamine infusion administered at a low dose intraoperatively on postoperative pain relief. Materials and Methods: Fifty-two patients belonging to American Society of Anesthesia (ASA) I/ASA II, scheduled for laparoscopic surgery were randomized into two groups (n = 26). Group A received 0.2 mg/kg bolus of ketamine before the skin incision followed by an infusion of 0.1 mg/kg/h throughout the period of surgery. Group B received an equal volume of saline bolus and infusion. Postoperative pain was assessed (Numerical Rating Scale [NRS] scale) every 30 min till 6 h. The time taken for first rescue analgesia, the total amount of opioid used, and degree of sedation postoperatively were also compared. Pain scores between the groups were compared using the Chi-square test. Results: Pain scores (NRS scores) over various time intervals postoperatively were significantly reduced in the ketamine group (P &lt; 0.001). The overall cumulative opioid consumption was significantly lower in the ketamine group compared to the placebo (69.29 ± 23.35 mg vs. 107.88 ± 35.21 mg, respectively, P = 0.008). There was also a significant difference in time to first rescue analgesia between the ketamine and placebo groups (2.60 ± 1.87 h vs. 0.43 ± 0.85 h, respectively, P = 0.001). Conclusion: Intraoperative low-dose ketamine infusion as an adjuvant significantly decreased postoperative pain with a reduced total dose of opioid consumption and a delayed time to first rescue analgesic.