Population Pharmacokinetics of Intravenous Lidocaine in Adults: A Systematic Review.

BACKGROUND: The establishment of optimal dosing regimens for intravenous (IV) lidocaine in the perioperative setting, aiming to balance effective pain relief with minimisation of potential side effects, is a topic of ongoing debate. This discussion stems from the significant variability in lidocaine's pharmacokinetic (PK) parameters and its relatively narrow safety margin. Population pharmacokinetic (popPK) modelling has emerged as a valuable tool for understanding the factors contributing to this observed variability in drug kinetics. OBJECTIVES: This systematic review compiles the existing knowledge on lidocaine's PK properties and published popPK models, with a focus on significant covariates. METHODS: A systematic search on Cochrane CENTRAL, Medline, and EMBASE was performed from inception to June 2023. Original clinical studies that administered IV lidocaine to adults and performed PK analyses using a nonlinear mixed effects modelling approach were included. The quality of the included studies was assessed by compliance with the Clinical Pharmacokinetics (ClinPK) statement checklist. RESULTS: Seven studies were included, which involved a diverse adult population, including both volunteers and patients with various comorbidities. Lidocaine PK was primarily characterised by a two- or three-compartment model. The volume of distribution at steady state ranged from 66 to 194 L, and the total clearance ranged from 22 to 49 L/h. Despite adjusting for significant covariates like heart failure status, alpha-1-acid glycoprotein, duration of lidocaine infusion, and body weight, each study revealed substantial variability in PK parameters. The potential impact of hepatic or renal function biomarkers on these PK parameters calls for further investigation. Incomplete reporting of key aspects of developed models may hinder the models' reliability and clinical application. CONCLUSION: The findings emphasise the importance of tailoring drug dosage to ensure the safe and effective use of intravenous lidocaine. Optimal design methodologies may be incorporated for a more efficient identification of important covariates. Utilising contemporary model evaluation methods like visual predictive checks and bootstrapping would enhance the robustness of popPK models and the reliability of their predictions. This comprehensive review advances our understanding of lidocaine's pharmacokinetics and lays the groundwork for further research in this critical area of perioperative pain management. Review protocol registered on 25 August 2023 in PROSPERO (CRD42023441113). This work was supported by the Fundamental Research Grant Scheme, the Ministry of Higher Education, Malaysia (FRGS/1/2020/SKK01/UM/02/2).

Quadratus Lumborum Block for Ovarian Cystectomy Surgery in a Patient With Severe Kyphoscoliosis.

Quadratus lumborum block (QLB) has been described as a regional analgesic technique in various abdominal surgeries. We present a case report of a high-risk patient who underwent ovarian cystectomy with QLB and deep sedation after failed neuraxial anesthesia. A 29-year-old female patient with comorbidities osteogenesis imperfecta, severe kyphoscoliosis with restrictive lung disease, and cervical syringomyelia with cranio-cervical junction stenosis (C2/C3). The patient had large ovarian cysts with associated dyspnea. She accepted surgery-an open bilateral ovarian cystectomy-despite being advised that general anesthesia would be high-risk. Regional anesthetic options were limited and challenging, given her anatomy and difficulty in positioning. Neuraxial anesthesia was attempted but was unsuccessful. The patient safely underwent surgery (lower midline laparotomy) using QLB. This clinically challenging case demonstrates the feasibility of QLB as the mainstay multimodal anesthetic approach (without general and neuraxial anesthesia) for abdominal surgery under exceptional circumstances.

Bispectral Index (BIS) Monitoring and Postoperative Delirium in Elderly Patients Undergoing Surgery: A Systematic Review and Meta-Analysis With Trial Sequential Analysis.

OBJECTIVE: To examine the effect of bispectral index (BIS)-guided anesthesia on the incidence of postoperative delirium (POD) in elderly patients undergoing surgery. DESIGN: A systematic review, meta-analysis, and trial sequential analysis (TSA). SETTING: In the operating room, postoperative anesthesia care units (PACU), and ward. PARTICIPANTS: Elderly patients (>60 years old) undergoing surgery. INTERVENTIONS: The EMBASE, MEDLINE, and CENTRAL databases were searched systematically from their inception until December 2020 for randomized controlled trials comparing BIS and usual care or blinded BIS. MEASUREMENTS AND MAIN RESULTS: Ten trials (N = 3,891) were included for quantitative meta-analysis. In comparison to the control group, there was no significant difference in the incidence of POD in elderly patients randomized to BIS-guided anesthesia (odds ratio [OR] 0.71, 95% CI 0.47-1.08, I2 = 76%, p = 0.11, level of evidence = very low, TSA = inconclusive). The authors' review demonstrated that elderly patients with BIS-guided anesthesia were significantly associated with a lower incidence of postoperative cognitive dysfunction (POCD) (OR 0.64, 95% CI 0.46-0.88, p = 0.006), extubation time (mean difference [MD] -3.38 minutes, 95% CI -4.38 to -2.39, p < 0.00001), time to eye opening (MD -2.17 minutes, 95% CI -4.21 to -0.14, p = 0.04), and time to discharge from the PACU (MD -10.77 minutes, 95% CI -11.31 to - 10.23, p < 0.00001). CONCLUSION: The authors' meta-analysis demonstrated that BIS-guided anesthesia was not associated with a reduced incidence of POD, but it was associated with a reduced incidence of POCD and improved recovery parameters.

Psychological distress among elderly surgical patients who had their surgery postponed during the COVID-19 pandemic.

BACKGROUND: Many institutions withheld elective lists and triaged surgeries during the peak of coronavirus disease 2019 (COVID-19) pandemic. As a result, older surgical patients have had to wait for rescheduled dates in a long waitlist. This study aimed to identify the psychological impact in these patients when they returned for surgery. METHODS: This was a cross-sectional study which included 153 patients aged ≥ 65 years undergoing elective surgery. Trained interviewers recruited and assessed psychological status pre-operatively with two validated questionnaires - Hospital Anxiety and Depression Scale (HADS) and 36-item Short Form Health Survey (SF-36). Specific questions were asked about their postponed surgeries, appetite and fear. RESULTS: A total of 36 out of 153 (23.5%) patients had their procedures deferred during the first wave of COVID-19 pandemic. Postponed cases were significantly based on the nature of surgery (p = 0.002), cancer diagnosis (p = 0.006) and surgical specialty (p = 0.023). Median HADS scores were higher for patients who were postponed (2.00 versus 4.00 for anxiety, p = 0.180 and 0.00 versus 1.00 for depression, p = 0.424) although no statistical significance was shown. In the whole study population, anxiety was a significant predictor for depression and vice versa (p < 0.001) with other predictive risk factors for anxiety that were age ≥ 85 years old (odds ratio [OR] 6.14, p = 0.018), female (OR 2.41, p = 0.024), cancer (OR 2.19, p = 0.039) and major surgery (OR 2.39, p = 0.023). Similarly, older patients ≥ 85 years old (OR 10.44, p = 0.003) and female (OR 6.07, p = 0.006) had higher risk for depression. Both anxiety and depression were significant risks for loss of appetite (p = 0.005 and 0.001). Lastly, the fear of disease progression due to rescheduling was more frequent in cancer patients (p = 0.035). CONCLUSION: The mental health and disease burden of older surgical patients should be taken into careful consideration when cases need to be postponed in our healthcare system.

Non-alcoholic fatty liver disease and obesity among adult donors are major challenges to living-donor liver transplantation: A single-center experience.

OBJECTIVES: Obesity and non-alcoholic fatty liver disease (NAFLD) are rampant in South East Asia. There is paucity of data exploring its' impact on donor suitability for living donor liver transplantation (LDLT). We aimed to describe and examine the factors related to non-utilization of potential donors in our LDLT programme. METHODS: This is an analysis of prospectively collected data on potential donors for an adult LDLT programme, between January 2017 and December 2019. RESULTS: Fifty-five donors for 33 potential recipients were evaluated. The mean age was 31.6 ± 8.5 years, 52.7% were female and the ethnic divisions were: Chinese (50.9%), Indian (25.5%) and Malay (23.6%). The mean body mass index (BMI) among potential donors was 25.1 ± 4.0 kg/m2; 25.5% of donors had normal BMI, 23.6% were overweight and 50.9% were obese. Using the CAP modality of Fibroscan®, we identified the following grades of hepatic steatosis: 36.6% S0, 19.5% S1, 2.4% S2 and 41.5% S3. The non-utilization rate of our donors was 74.5% (41/55) and the main reasons were significant hepatic steatosis and/or obesity. Compared to suitable donors, unsuitable donors had significantly greater mean BMI, mean CAP scores, higher rates of dyslipidaemia and NAFLD. CONCLUSION: NAFLD and obesity represent major challenges to an emerging LDLT programme in Malaysia.

Transversus Abdominis Plane Block Versus Intraperitoneal Local Anesthetics in Bariatric Surgery: A Systematic Review and Network Meta-analysis.

BACKGROUND: Transversus abdominis plane (TAP) block and intraperitoneal local anesthetics (IPLA) are widely investigated techniques that potentially improve analgesia after bariatric surgery. The analgesic efficacy of TAP block has been shown in previous studies, but the performance of TAP block can be difficult in patients with obesity. We performed a systematic review and meta-analysis to compare the analgesic efficacy of TAP block and IPLA. An alternative technique is useful in clinical setting when TAP block is not feasible. METHODS: We searched PubMed, Embase, and CENTRAL from inception until August 2020 for randomized controlled trials comparing both techniques. The primary outcome was cumulative morphine consumption at 24 h. Secondary pain-related outcomes included pain score at rest and on movement at 2, 6, 12, and 24 h; postoperative nausea and vomiting; and length of hospital stay. RESULTS: We included 23 studies with a total of 2,178 patients. TAP block is superior to control in reducing opioid consumption at 24 h, improving pain scores at all the time points and postoperative nausea and vomiting. The cumulative opioid consumption at 24 h for IPLA is less than control, while the indirect comparison between IPLA with PSI and control showed a significant reduction in pain scores at rest, at 2 h, and on movement at 12 h, and 24 h postoperatively. CONCLUSIONS: Transversus abdominis plane block is effective for reducing pain intensity and has superior opioid-sparing effect compared to control. Current evidence is insufficient to show an equivalent analgesic benefit of IPLA to TAP block.

Reversal of residual neuromuscular block with neostigmine or sugammadex and postoperative pulmonary complications: a prospective, randomised, double-blind trial in high-risk older patients.

BACKGROUND: Residual neuromuscular block is associated with an increased risk of postoperative pulmonary complications in retrospective studies. The aim of our study was to investigate prospectively the incidence of postoperative pulmonary complications after reversal with either sugammadex (SUG) or neostigmine (NEO) in high-risk older patients. METHODS: We randomly allocated 180 older patients with significant morbidity (ASA physical status 3) ≥75 yr old to reversal of rocuronium with either SUG or NEO. Adverse events in the recovery room and pulmonary complications (defined by a 5-point [0-4; 0=best to 4=worst] outcome score) on postoperative Days 1, 3, and 7 were compared between groups. RESULTS: Data from 168 patients aged 80 (4) yr were analysed; SUG vs NEO resulted in a reduced probability (0.052 vs 0.122) of increased pulmonary outcome score (impaired outcome) on postoperative Day 7, but not on Days 1 and 3. More patients in the NEO group were diagnosed with radiographically confirmed pneumonia (9.6% vs 2.4%; P=0.046). The NEO group showed a non-significant trend towards longer hospital length of stay across all individual centres (combined 9 vs 7.5 days), with a significant difference in Malaysia (6 vs 4 days; P=0.011). CONCLUSIONS: Reversal of rocuronium neuromuscular block with SUG resulted in a small, but possibly clinically relevant improvement in pulmonary outcome in a select cohort of high-risk older patients. CLINICAL TRIAL REGISTRATION: ACTRN12614000108617.

Comparison of deep and moderate neuromuscular blockade in microwave ablation of liver tumours: a randomized-controlled clinical trial.

Microwave ablation (MWA) is gaining popularity for the treatment of small primary hepatocellular carcinoma and metastatic lesions especially if patients are not candidates for surgical resection. Deep neuromuscular blockade (DMB) is perceived to improve surgical working conditions compared to moderate neuromuscular blockade (MMB) but no studies have examined the same benefits in MWA of liver tumours. This study aimed to compare the clinical outcomes of DMB and MMB in MWA of liver tumours in terms of liver excursion, performance scores by the interventional radiologists and patients, requirements of additional muscle relaxants and complications. 50 patients were recruited and 45 patients (22 in MMB group, 23 in DMB group) completed the study. The mean liver excursion for the MMB group (1.42 ± 1.83 mm) was significantly higher than the DMB group (0.26 ± 0.38 mm) (p = 0.001). The mean Leiden-Surgical Rating Scale (L-SRS) rated by the two interventional radiologists were 4.5 ± 0.59 and 3.6 ± 0.85 for the DMB and MMB groups, respectively (p = 0.01). There was also statistically significant difference on patient satisfaction scores (0-10: Extremely Dissatisfied-Extremely Satisfied) between DMB (8.74 ± 1.1) and MMB (7.86 ± 1.25) groups (p = 0.01). 5 patients from MMB group and none from DMB group required bolus relaxant during the MWA procedure. Adverse events were also noted to be more severe in the MMB group. In conclusion, DMB significantly reduced liver excursion and movement leading to improved accuracy, safety and success in ablating liver tumour.

The hemodynamic and pain impact of peripheral nerve block versus spinal anesthesia in diabetic patients undergoing diabetic foot surgery.

PURPOSE: Comparison of hemodynamic profiles and pain scores in diabetic patients undergoing diabetic foot surgery receiving peripheral nerve block (PNB) or spinal anesthesia [subarachnoid block (SAB)]. METHODS: This was a prospective, randomised controlled trial. We recruited diabetic patients aged > 18 years, American Society of Anesthesiologists class II-III, who were scheduled for unilateral diabetic foot surgery below the knee. All patients were assessed for autonomic dysfunction using the Survey of Autonomic Symptoms score. Participants were randomly assigned to receive either PNB or SAB for the surgery. Hemodynamic data, including usage of vasopressors, were recorded at 5-min intervals for up to 1 h after the induction of anesthesia. Pain scores were recorded postoperatively, and follow-up was done via telephone 6 months later. RESULTS: Compared to the PNB group, the SAB group had a larger number of patients with significant hypotension (14 vs. 1; p = 0.001) and more patients who required vasopressor boluses (6 vs. 0 patients). Compared to SAB group, the patients in the PNB group had a longer postoperative pain-free duration (9 vs. 4.54 h; p = 0.002) and lower pain scores 1 day after surgery (3.63 vs. 4.69; p = 0.01). CONCLUSION: Peripheral nerve block should be considered, whenever possible, as the first option of anesthesia for lower limb surgery in diabetic patients as it provides hemodynamic stability and superior postoperative pain control compared to SAB. TRIAL REGISTRATION: Clinical trial registry: ClinicalTrials.gov. ID NCT02727348.

Rationale and design for the detection and neurological impact of cerebrovascular events in non-cardiac surgery patients cohort evaluation (NeuroVISION) study: a prospective international cohort study.

OBJECTIVES: Covert stroke after non-cardiac surgery may have substantial impact on duration and quality of life. In non-surgical patients, covert stroke is more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac surgery.NeuroVISION is a multicentre, international, prospective cohort study that will characterise the association between perioperative acute covert stroke and postoperative cognitive function. SETTING AND PARTICIPANTS: We are recruiting study participants from 12 tertiary care hospitals in 10 countries on 5 continents. PARTICIPANTS: We are enrolling patients ≥65 years of age, requiring hospital admission after non-cardiac surgery, who have an anticipated length of hospital stay of at least 2 days after elective non-cardiac surgery that occurs under general or neuraxial anaesthesia. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients are recruited before elective non-cardiac surgery, and their cognitive function is measured using the Montreal Cognitive Assessment (MoCA) instrument. After surgery, a brain MRI study is performed between postoperative days 2 and 9 to determine the presence of acute brain infarction. One year after surgery, the MoCA is used to assess postoperative cognitive function. Physicians and patients are blinded to the MRI study results until after the last patient follow-up visit to reduce outcome ascertainment bias.We will undertake a multivariable logistic regression analysis in which the dependent variable is the change in cognitive function 1 year after surgery, and the independent variables are acute perioperative covert stroke as well as other clinical variables that are associated with cognitive dysfunction. CONCLUSIONS: The NeuroVISION study will characterise the epidemiology of covert stroke and its clinical consequences. This will be the largest and the most comprehensive study of perioperative stroke after non-cardiac surgery. TRIAL REGISTRATION NUMBER: NCT01980511; Pre-results.

Combining glidescope and fiber-optic for intubation in oral maxillofacial surgery.

Airway management for patients with recent oral facial injuries is always a challenge for the anesthetist. We describe how the glidescope (GLS) and fiber-optic (FOB) can be effectively combined in three patients undergoing oral maxillofacial surgeries after sustaining multiple facial fractures from trauma to allow less traumatic intubation, an option to visualize on either monitor and faster intubating time (mean 1 min 14 s for our cases) compared to the use of either one alone. Although it allows for better visualization of the vocal cords, it requires 2 trained anaesthetists to perform and this would need to be considered when using this technique.

Effects of immunonutrition on biomarkers in traumatic brain injury patients in Malaysia: a prospective randomized controlled trial.

BACKGROUND: Head injury is one of the top three diagnosis leading to intensive care unit (ICU) admission in Malaysia. There has been growing interest in using immunonutrition as a mode of modulating the inflammatory response to injury or infection with the aim of improving clinical outcome. The aim of the present study was to evaluate the effect of an immunonutrition on biomarkers (IL-6, glutathione, CRP, total protein and albumin) in traumatic brain injury patients. METHODS: Thirty six patients with head injury admitted to neurosurgical ICU in University Malaya Medical Centre were recruited for this study, over a 6-month period from July 2014 to January 2015. Patients were randomized to receive either an immunonutrition (Group A) or a standard (Group B) enteral feed. Levels of biomarkers were measured at day 1, 5 and 7 of enteral feeding. RESULTS: Patients in Group A showed significant reduction of IL-6 at day 5 (p < 0.001) with concurrent rise in glutathione levels (p = 0.049). Patients in Group A also demonstrated a significant increase of total protein level at the end of the study (day 7). CONCLUSION: These findings indicate the potential of immunonutrition reducing cytokines and increasing antioxidant indices in patients with TBI. However, further studies incorporating patient outcomes are needed to determine its overall clinical benefits. TRIAL REGISTRATION: National Medical Research Register (NMRR) ID: 14-1430-23,171. ClinicalTrials.gov identifier: NCT03166449 .

Comparing the efficacy and safety between propofol and dexmedetomidine for sedation in claustrophobic adults undergoing magnetic resonance imaging (PADAM trial).

STUDY OBJECTIVE: To determine the efficacy of sedation with dexmedetomidine compared to propofol for claustrophobic adults undergoing magnetic resonance imaging (MRI) in our institution. DESIGN: Randomized, prospective, double-blinded study. SETTING: University-based tertiary referral center. PATIENTS: Thirty claustrophobic adults with American Society of Anesthesiologists physical status I and II who were planned for MRI. INTERVENTIONS: Patients were randomly assigned to target-controlled infusion propofol or dexmedetomidine loading followed by maintenance dose for procedural sedation. MEASUREMENTS AND MAIN RESULTS: The primary end point was adequate reduction in patient anxiety levels to allow successful completion of the MRI sequence. Both methods of sedation adequately reduced anxiety levels in visual analog scale scores and Spielberger Strait Test Anxiety Inventory (P<.001). Dexmedetomidine required a longer time to achieve anxiolysis, 7.36minutes (SD, 2.59), and required increasing maintenance dose to induce sleep compared to 10.71minutes (SD, 4.63) for propofol. In terms of image quality, 2 patients (16.67%) in the dexmedetomidine group were satisfactory, whereas all with propofol were graded as good to excellent. Adverse effects were seen in patients sedated with dexmedetomidine with number needed to harm 8 for hypotension and 15 for bradycardia compared to none recorded in the propofol arm. There was no significant difference in patient satisfaction scores or home readiness after the MRI. CONCLUSIONS: Both dexmedetomidine and propofol can effectively reduce anxiety levels of claustrophobic adults undergoing MRI, but dexmedetomidine takes longer to achieve adequate anxiolysis and sleep and may have an effect on image quality. Hypotension and bradycardia are common adverse effects observed with dexmedetomidine.

Handedness in man: The energy availability hypothesis.

More than 90% of the human species are right handed. Although outwardly our body appears symmetrical, a 50/50% lateralization in handedness never occurs. Neither have we seen more than 50% left handedness in any subset of the human population. By 12-15weeks of intrauterine life, as many as 6 times more fetuses are noted by ultrasound studies to be sucking on their right thumbs. Distinct difference in oxygenation leading to dissimilar energy availability between right and left subclavian arteries in place by week 9 of life may hold the clue to the lateralization of hand function and eventually, the same in the brain. We know there is a higher incidence of left handedness in males, twins, premature babies and those born to mothers who smoke. They may represent a subset with less distinct difference in oxygenation between the 2 subclavian arteries during the fetal stage. This hypothesis if correct not only closes the gap in understanding human handedness and lateralization but also opens a vista for new research to focus on in utero tissue energy availability and its impact on outcome in life.