Perioperative Administration Research Articles

Perioperative oxygen therapy: a protocol for an overview of systematic reviews and meta-analyses

BackgroundOxygen is routinely given to patients during and after surgery. Perioperative oxygen administration has been proposed as a potential strategy to prevent and treat hypoxaemia and reduce complications, such as surgical site infections, pulmonary complications and mortality. However, uncertainty exists as to which strategies in terms of amount, delivery devices and timing are clinically effective. The aim of this overview of systematic reviews and meta-analyses is to answer the research question, ‘For which types of surgery, at which stages of care, in which sub-groups of patients and delivered under what conditions are different types of perioperative oxygen therapy clinically effective?’.MethodsWe will search key electronic databases (MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CENTRAL, Epistemonikos, PROSPERO, the INAHTA International HTA Database and DARE archives) for systematic reviews and randomised controlled trials comparing perioperative oxygen strategies.Each review will be mapped according to type of surgery, surgical pathway timepoints and clinical comparison. The highest quality reviews with the most comprehensive and up-to-date coverage of relevant literature will be chosen as anchoring reviews. Standardised data will be extracted from each chosen review, including definition of oxygen therapy, summaries of interventions and comparators, patient population, surgical characteristics and assessment of overall certainty of evidence. For clinical outcomes and adverse events, the overall pooled findings and results of subgroup and sensitivity analyses (where available) will be extracted. Trial-level data will be extracted for surgical site infections, mortality, and potential trial-level effect modifiers such as risk of bias, outcome definition and type of surgery to facilitate quantitative data analysis. This analysis will adopt a multiple indication review approach with panoramic meta-analysis using review-level data and meta-regression using trial-level data. An evidence map will be produced to summarise our findings and highlight any research gaps.DiscussionThere is a need to provide a panoramic overview of systematic reviews and meta-analyses describing peri-operative oxygen practice to both inform clinical practice and identify areas of ongoing uncertainty, where further research may be required. Systematic review registrationPROSPERO CRD42021272361

Levosimendan in paediatric cardiac anaesthesiology: A systematic review and meta-analysis.

Low cardiac output syndrome (LCOS) after congenital cardiac surgery has an incidence of up to 25%. Preventing and treating LCOS is of pivotal importance as LCOS is associated with excess morbidity and mortality. This systematic review assesses the safety and efficacy of peri-operative levosimendan administration in the setting of paediatric cardiac surgery. Systematic review of randomised controlled trials. Meta-analyses were performed on efficacy and exploratory outcomes. Literature was searched in the following databases (MEDLINE, EMBASE, Web of Science and CENTRAL) from inception to July 2021. Randomised controlled trials comparing levosimendan with other inotropes or placebo in children younger than 18 years of age undergoing cardiac surgery. Nine studies enrolling a total of 539 children could be included in the systematic review. All trials study the prophylactic administration of levosimendan in comparison with placebo ( n = 2), milrinone ( n = 6) or dobutamine ( n = 1). Levosimendan dosing varied considerably with only three studies using a loading dose. Levosimendan reduced the incidence of LCOS [risk ratio (RR) 0.80] [95% confidence interval (CI), 0.40 to 0.89, P = 0.01] and increased cardiac index (MD 0.17 l min -1 m -2 ) (95% CI, 0.06 to 0.28, P = 0.003) without affecting other outcomes (mortality, ICU length of stay, hospital length of stay, duration of mechanical ventilation, serum lactate, central venous oxygen saturation, serum creatine or acute kidney injury). The prophylactic use of levosimendan in children undergoing cardiac surgery reduced the incidence of LCOS and increased cardiac index compared with other inotropes or placebo. This effect did not translate into an improvement of other clinical endpoints.

Male gender, smoking, younger age, and preoperative pain found to increase postoperative opioid requirements in 592 elective colorectal resections.

With increased awareness of the opioid epidemic, understanding contributing factors to postoperative opioid use is important. The purpose of this study was to evaluate patient and perioperative factors that contribute to postoperative opioid use after colorectal resections and their relation to pre-existing pain conditions and psychiatric diagnoses. A retrospective review was conducted identifying adult patients who underwent elective colorectal resection at a single tertiary center between 2015 and 2018. Patient demographics, preoperative factors, surgical approach, and perioperative pain management were evaluated to determine standard conversion morphine milligram equivalents required for postoperative days 0 to 3 and total hospital stay. Five hundred and ninety-two patients: 46% male, median age 58years undergoing colorectal resections for indications including cancer, inflammatory bowel disease, and diverticulitis were identified. Less opioid use was found to be associated with female gender (β = - 42), patients who received perioperative lidocaine infusion (β = - 30), and older adults (equivalents/year) (β = - 4, all p < 0.01). Preoperative opioid use, preoperative abdominal pain, epidural use, and smoking were all independently associated with increased postoperative opioid requirements. In this study of patients undergoing elective colorectal resection, factors that were associated with higher perioperative opioid use included male gender, smoking, younger age, preoperative opioid use, preoperative abdominal pain, and epidural use. Perioperative administration of lidocaine was associated with decreased opioid requirements. Understanding risk factors and stratifying postoperative pain regimens may aid in improved pain control and decrease long-term dependency.

Dexamethasone and clinically significant postoperative nausea and vomiting: a prespecified substudy of the randomised perioperative administration of dexamethasone and infection (PADDI) trial

BackgroundClinically significant postoperative nausea and vomiting (PONV) is a patient-reported outcome which reflects patient experience. Although dexamethasone prevents PONV, it is unknown what impact it has on this experience. MethodsIn this prespecified embedded superiority substudy of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and completed a validated PONV questionnaire. The primary outcome was the incidence of clinically significant PONV on day 1 or day 2 postoperatively. Secondary outcomes included the incidence of clinically significant PONV and severe PONV on days 1 and 2 considered separately. ResultsA total of 1466 participants were included, with 733 patients allocated to the dexamethasone arm and 733 to matched placebo. The primary outcome occurred in 52 patients (7.1%) in the dexamethasone arm and 66 (9%) patients in the placebo arm (relative risk [RR]=0.79; 95% confidence interval [CI], 0.56–1.11; P=0.18). Severe PONV occurred on day 2 in 27 patients (3.9%) in the dexamethasone arm and 47 patients (6.7%) in the placebo arm (RR=0.58; 95% CI, 0.37–0.92; P=0.02; number needed-to-treat (NNT)=36.7; 95% CI, 20–202). In the entire cohort of 8880 PADDI patients, lower nausea scores, less frequent administration of antiemetics, and fewer vomiting events were recorded by patients in the dexamethasone arm up to day 2 after surgery. ConclusionsAdministration of dexamethasone 8 mg i.v. did not influence clinically significant PONV. Dexamethasone administration did, however, decrease the incidence and severity of PONV, and was associated with less frequent administration of antiemetic agents. Clinical trial registrationACTRN12614001226695.

Effect of Perioperative Dexmedetomidine Infusion on Postoperative Delirium in Elderly Patients Undergoing Oral and Maxillofacial Surgery: A Randomized Controlled Clinical Trial.

PurposeThe aim of the study was to determine whether perioperative dexmedetomidine administration can improve postoperative delirium in elderly patients undergoing oral and maxillofacial surgery.Patients and MethodsThis was a prospective double-blind randomized controlled clinical trial conducted in Cangzhou Central Hospital from December 2021 to March 2022. Patients aged 65 and older underwent oral and maxillofacial surgery under general anesthesia. Eligible patients were randomly assigned to dexmedetomidine or control group. Dexmedetomidine was injected intravenously from 10 min before induction of anesthesia to 30 min before the end of surgery in dexmedetomidine group, while patients in the control group were given normal saline at the same rate during the same time period. The primary measurement indicators were the incidence and duration of delirium in the first five days after surgery. The secondary measurement indicators were Visual Analogue Score (VAS) for the first 24 hours following surgery, subjective sleep quality score within 24 hours postoperatively and intraoperative adverse reactions.ResultsOne hundred and twenty patients were randomly assigned. Baseline characteristics were similar between two groups. The incidence and duration of postoperative delirium did not differ statistically between two groups (all P > 0.05). Compared with control group, VAS scores in dexmedetomidine group were significantly lower at 6, 12, and 24 hours after surgery (all P < 0.05); moreover, Richards-Campbell Sleep Questionnaire (RCSQ) results were significantly improved 1 day after surgery in dexmedetomidine group (P < 0.05). Dexmedetomidine-related adverse reactions were similar in both groups (P > 0.05).ConclusionIntravenous infusion of dexmedetomidine 10 min before induction of anesthesia to half an hour before the end of surgery did not improve postoperative delirium in elderly patients undergoing oral and maxillofacial surgery; however, dexmedetomidine may be associated with decreased postoperative pain and improved postoperative sleep quality.

Preoperative transversus abdominis plane block decreases intraoperative opiate use during pancreatoduodenectomy.

Multimodal analgesia and regional anesthetic blocks, such as transversus abdominis plane (TAP) block, decrease postoperative opiate consumption but their effect on intraoperative opiates is unknown. This was a retrospective review of patients undergoing pancreatoduodenectomy between June 2018 and February 2021, in which perioperative data, operative times, and medication administration data were collected. Intraoperative opiate use was calculated in total morphine equivalent doses (MED) for each patient and adjusted for operative time. Univariate analysis and multivariate linear regression were performed to determine factors affecting intraoperative opiate requirements. Of the 169 patients in the study, 51 (30.2%) received pre-surgical TAP blocks and 118 (69.8%) did not. There were no statistically significant differences in intraoperative opiate use with preoperative acetaminophen (p=0.527), celecoxib (p=0.553), gabapentin (p=0.308), intraoperative ketorolac (p=0.698) or epidural placement (p=0.086). Minimally invasive surgery had lower intraoperative opiate use compared to open (p=0.011), as well as pre-surgical TAP block compared to no pre-surgical block (5.24 vs 7.27 MED/hour, p<0.001). On multivariate linear regression, pre-surgical TAP block (p=0.001) was independently associated with decreased intraoperative opiate use. Preoperative TAP blocks were associated with decreased intraoperative opiate use during pancreatoduodenectomy and should be considered for routine use.

Intraoperative methadone: Proceed with care.

A recent review suggests minimal respiratory depression (RD) after perioperative methadone, while another identified RD in up to 37 percent of patients. A meta-analysis is equivocal. At our institution, five of 75 opioid naive patients (6.6 percent) given perioperative methadone received naloxone. We report three of these cases in detail. Two others were discovered during an electronic medical record search for opioid naïve patients who received methadone plus naloxone during their anesthesia care. Our five patients indicate that RD owing to methadone can occur with excessive perioperative adjuvant medications and/or in patients who are taking home central nervous system depressants. We define perioperative adjuvant medications as medications given by the anesthesiologist prior to induction and intraoperatively. The risks and benefits of perioperative methadone administration, specifically in patients who received post-operative naloxone, deserve further investigation.

Abstract CT507: ATP128 vaccine with ezabenlimab promotes antigen-specific immune responses in stage IV colorectal cancer in the KISIMA-01 phase 1b trial

Abstract Background: KISIMA࣪ is a vaccine platform based on a single chimeric fusion protein, containing a proprietary cell-penetrating peptide (CPP) for antigen delivery, a proprietary Toll-like receptor (TLR)-peptide agonist with self-adjuvant properties and a modulable multi-antigenic domain (Mad). ATP128 vaccine targets 3 antigens: carcinoembryonic antigen (CEA), Survivin and Achaete-scute complex homolog 2 (ASCL2); it is used in combination with a PD-1 inhibitor in the treatment of MSS/MMR proficient stage IV colorectal cancer (CRC) patients, after first line of standard of care therapy or as perioperative administration in patients with resectable liver metastases. Method: KISIMA-01 (NCT04046445) is an open-label, multi-center Phase 1b trial to investigate the safety, tolerability and immunogenicity of AT128 alone or in combination with the anti-PD-1 antibody ezabenlimab in patients with stage IV CRC. ATP128 is given SC q2w for the first 3 immunizations (prime) and q4w for the last 3 immunizations (boost). Ezabenlimab is administered q3w starting with the first ATP128 administration. Blood and tissue samples are collected before, during and after ATP128 treatment to monitor the induction of a tumor associated antigen-specific immune response (ELISpot) and immune-related changes in the peripheral blood and in the tumor microenvironment by immunohistochemistry (IHC) and flow cytometry. Results: In more than 50% of evaluated patients treated with ATP128 alone or with ezabenlimab, a cellular immune response against at least one out of three antigens was observed as determined by IFN-γ ELISpot analyses of patient PBMCs after the 3rd vaccination. Analysis of liver metastases by IHC indicated that evaluated patients were positive for all 3 antigens in ATP128. Furthermore, for the patients with paired biopsies, a significant increase in CD8 T cells infiltration into the tumor parenchyma was observed after 3 vaccine administrations, along with a significantly higher proportion of CD45RO expressing memory cells within the CD4 population as compared to baseline. Tumor infiltrating lymphocytes (TILs) flow cytometry analysis comparing untreated (historical controls) and ATP128/ezabenlimab-treated patients showed a similar quantity of the different infiltrated subsets but an improved quality of infiltrated T cells, indicated by an increase (more than 2-fold) in proportion of central memory T cells and an impressive decrease of the proportion of cells positive for exhaustion markers expression in KISIMA-01 patients. Conclusions: Analyses indicate induction of ATP128-specific immune response in the peripheral circulation and increased infiltration of TILs into liver metastases with an improved quality of T cells. Citation Format: Heinz-Josef Lenz, Hanz Prenen, Eric Van Cutsem, Thibaud Kössler, Jean-François Mayol, Francesca Trapani, Matthieu Tihy, Laura Rubbia-Brandt, Christian Toso, Thomas Bogenrieder, Elodie Belnoue, Madiha Derouazi, Scott Kopetz. ATP128 vaccine with ezabenlimab promotes antigen-specific immune responses in stage IV colorectal cancer in the KISIMA-01 phase 1b trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT507.

The effect of anesthesia without opioid on perioperative opioid demand in children with severe obstructive sleep apnea (OSA) for adenotonsillectomies — single-center retrospective observational study

BackgroundChildren with severe obstructive sleep apnea (OSA) carry a higher risk of respiratory complications after adenotonsillectomy. Their altered sensitivity to opioids may be a significant contributor to respiratory morbidity. The purpose of this study was to identify how anesthesia without opioids affects perioperative opioid demand and postoperative course.MethodsA chart review of children with severe OSA (apnea hypoxia index; AHI ≥ 10) undergoing adenotonsillectomies was performed. Comorbidities and perioperative medications were documented. Perioperative opioid doses within 48 h of procedure were calculated as morphine equivalents (mcg/kg). Pain scores, rescue medications, and postoperative complications in PICU and non-PICU settings were also documented. Anesthesia without opioid and with opioid groups were compared.ResultsThe analysis included 225 children. A significantly higher percentage of children received no postoperative opioids in the anesthesia without opioid group compared to those with opioid (46 of 88 children vs. 43 of 137; P < 0.05). The incidence of severe postoperative pain between the two groups was not different in PICU (P = 0.88) or non-PICU setting (P = 0.84). Perioperative opioid administration was significantly lower in anesthesia without opioid (median, Q1, Q3: 0.0, 0.0, 83.0) compared to with opioid (144.4, 72.5, 222.2; P < 0.01). Anesthesia without opioid was one of the independent factors to achieve perioperative opioid avoidance (<50mcg/kg).ConclusionsAnesthesia without opioid for children with severe OSA for tonsillectomy significantly reduced perioperative demand for opioid and did not affect the occurrence of severe pain. Anesthesia without opioid is an effective strategy to minimalize opioid demand perioperatively for children with severe OSA for tonsillectomy.

A phase I clinical trial on intracranial administration of autologous myeloid dendritic cells (myDC) in combination with ipilimumab and nivolumab in patients with recurrent glioblastoma (rGB).

2033 Background: Intracerebral administration of ipilimumab (IPI) and nivolumab (NIVO) following resection of rGB was demonstrated to be safe and resulted in encouraging survival (Duerinck, Schwarze et al. JITC 2021; Neyns et al. ESMO 2021). CD1c(BDCA-1)+ and CD141(BDCA-3)+ myDC play a pivotal role in initiating an adaptive anti-tumor immune response by re-licensing cytotoxic T lymphocytes within the tumor microenvironment. Methods: Eligible patients (pts)(diagnosed with rGB following radiation and temozolomide treatment; not in need of steroids) underwent a leukapheresis followed by immunomagnetic bead isolation and cryopreservation of CD1c (BDCA-1)+ / CD141(BDCA-3)+ myDC. At the time of surgery, an escalating number of myDC (1, 10, and 20x106 myDC) were injected into the brain tissue lining the resection cavity following maximal safe resection of the rGB (ICer) or injected intratumorally (ITum) following stereotactic biopsy (STx). IPI (5 mg) plus NIVO (10 mg) were co-injected with myDC. NIVO was administered intracavitary (ICav, 10mg) using an Ommaya port and intravenously (IV, 10mg) Q2w (max 12x). Results: Fourteen pts (9 male; median 48y [range 20-78]) were recruited (resection n = 11; STx n = 2) and underwent a successful leukapheresis and isolation of myDC; peroperative administration of myDC was preceded by resection in 10 pts (1 pt did not undergo surgery due to clinical deterioration/cerebral edema), and by STx in 2 pts. Respectively 6 (incl both pts who underwent a STx), 3, and 4 pts were treated at the 3 dose levels. All pts received ITum/ICer/IV-administrations of IPI and NIVO as planned. Median number of postoperative ICav/IV NIVO-administrations was 7 (range 2-11). Most frequent adverse events (AE) were headache (n = 11), fatigue (n = 9), transient dysphasia (n = 6), and nausea (n = 5). Bacterial colonization of the Ommaya occurred in 3 pts necessitating removal. Immune-related AE were infrequent and mild. No G5 AE occurred. No dose-limiting toxicities were seen with increasing numbers of myDC. After a median follow-up of 54w, 3 pts remain progression-free (after 42+, 51+, 54+ weeks of FU), 6 (46%) pts have died; median PFS is 13w (95% CI 0-26), median OS has not been reached; 6-months PFS- and OS-rate are respectively 30% and 84%, 12-months PFS- and OS-rate are respectively 23% and 51%. OS compares favorably to an historical cohort of Belgian rGB patients (n = 469; Log-Rank p = 0.018). Gene expression profiling of resected tissue, analysis of cellular counts, cytokines, NIVO/IPI-concentrations in on-treatment cerebrospinal fluid samples is ongoing. Conclusions: Intracranial administration of autologous myDC plus IPI and NIVO in combination with IV NIVO was found to be feasible, sufficiently safe and associated with encouraging survival justifying further investigation in pts with resectable rGB. Clinical trial information: NCT03233152.

Perioperative Administration of Cystine and Theanine Suppresses Inflammation and Facilitates Early Rehabilitation and Recovery after Esophagectomy: A Randomized, Double-Blind, Controlled Clinical Trial.

Oral administration of cystine and theanine (CT) increases glutathione levels to modulate the inflammatory response, which has yet to be sufficiently explored for patients’ recovery and early rehabilitation. We planned a randomized, double-blind, placebo-controlled trial to determine whether perioperative oral administration of CT promotes recovery after esophagectomy. Patients were randomized into either CT or placebo groups, who received preoperative and postoperative treatments for 4 and 13 days, respectively. The main outcome measures were triaxial accelerometer readings, inflammation indicators, a 6 min walk test (6MWT), and a quality of life questionnaire (QoR-40). The study involved 32 patients. Although the CT group (n = 16) showed better patient activity across the investigated period, there was no significant difference between the two groups. However, white blood cell count on postoperative days (POD) 2 and 10, neutrophil count (POD 2, 7, and 10), and C-reactive protein level (POD 13) in the CT group were significantly lower than in the placebo group. Furthermore, 6MWT on POD 7 and QoR-40 on POD 13 were significantly higher in the CT group than those in the placebo group. This study suggests that perioperative administration of CT may contribute to early recovery and rehabilitation after esophagectomy via suppression of inflammatory response.

Effect of perioperative lignocaine infusion on postoperative pain relief for laparoscopic intraperitoneal onlay mesh repair: A randomized controlled study.

The focus on enhanced recovery after surgery (ERAS) and opioid-free anesthesia has renewed interest in use of lignocaine. We evaluated postoperative pain relief following intravenous (IV) lignocaine administration in patients undergoing laparoscopic intraperitoneal onlay mesh repair (IPOM). Seventy patients were randomized into two groups. Group L patients were administered IV lignocaine infusion (1.5mg/kg) at induction of anesthesia followed by infusion (1.5mg/kg/h), until 1hour in the post-anesthesia care unit (PACU). Group P patients received equal volumes of normal saline IV infusion. We recorded hemodynamics, perioperative analgesic consumption, postoperative visual analog scores (VAS), incidence of postoperative nausea and vomiting (PONV), bowel function, patient satisfaction and length of hospital stay (LOS). The hemodynamics in both groups were maintained. Group L had lower VAS scores as compared to Group P (P < .05). Intraoperative fentanyl consumption in Group L was significantly less than Group P (P=.029). Group L patients scored lower on the Likert scale in comparison to the patients of Group P at 0hour (P=.013). Recovery of bowel function as assessed by time to pass first flatus was significantly shortened by IV lignocaine (P=.001). The perioperative administration of IV lignocaine resulted in decreased postoperative analgesic requirement and greater patient satisfaction scores. Perioperative IV lignocaine infusion provided good pain relief, hemodynamic stability and decreased perioperative analgesic consumption. PONV incidence decreased along with an early return of bowel function, reduced LOS and improved patient satisfaction in patients undergoing laparoscopic IPOM surgery.

Effect of adjuvant therapy with teriparatide in patients with thoracolumbar osteoporotic vertebral fractures who underwent vertebroplasty with posterior spinal fusion

Teriparatide (TPTD) administration has a potent osteogenic action and promotes the healing of osteoporotic vertebral fractures (OVFs). We aimed to investigate the outcomes of vertebroplasty with posterior spinal fusion (VP + PSF) and determine the impact of perioperative TPTD administration. We included 73 patients (18 male and 55 female patients; mean age: 78 years) with thoracolumbar OVFs who underwent VP + PSF and were followed-up for at least 2 years. Twenty-three patients who received TPTD perioperatively for > 3 months were included in the TPTD group, and the remaining 50 patients were included in the non-TPTD group. Radiographic findings regarding sagittal alignment and clinical outcomes in both groups were compared. The mean duration of TPTD administration was 17.5 ± 5.0 months (range 4–24 months). The mean loss of correction of local kyphosis angle in the TPTD group (4.0°) was lesser than that in the non-TPTD group (7.5°; p < 0.05); however, no significant differences were observed between the groups regarding global sagittal alignment, the occurrence of subsequent vertebral fractures, pedicle screw loosening and treatment-efficacy rates of clinical outcomes. Local kyphosis correction in patients who underwent VP + PSF for OVFs could be maintained through perioperative TPTD administration; however, TPTD administration had little effect on clinical outcomes.

Perioperative Suppression of Schwann Cell Dedifferentiation Reduces the Risk of Adenomyosis Resulting from Endometrial-Myometrial Interface Disruption in Mice.

We have recently demonstrated that endometrial–myometrial interface (EMI) disruption (EMID) can cause adenomyosis in mice, providing experimental evidence for the well-documented epidemiological finding that iatrogenic uterine procedures increase the risk of adenomyosis. To further elucidate its underlying mechanisms, we designed this study to test the hypothesis that Schwann cells (SCs) dedifferentiating after EMID facilitate the genesis of adenomyosis, but the suppression of SC dedifferentiation perioperatively reduces the risk. We treated mice perioperatively with either mitogen-activated protein kinase kinase (MEK)/extracellular-signal regulated protein kinase (ERK) or c-Jun N-terminal kinase (JNK) inhibitors or a vehicle 4 h before and 24 h, 48 h and 72 h after the EMID procedure. We found that EMID resulted in progressive SCs dedifferentiation, concomitant with an increased abundance of epithelial cells in the myometrium and a subsequent epithelial–mesenchymal transition (EMT). This EMID-induced change was abrogated significantly with perioperative administration of JNK or MEK/ERK inhibitors. Consistently, perioperative administration of a JNK or a MEK/ERK inhibitor reduced the incidence by nearly 33.5% and 14.3%, respectively, in conjunction with reduced myometrial infiltration of adenomyosis and alleviation of adenomyosis-associated hyperalgesia. Both treatments significantly decelerated the establishment of adenomyosis and progression of EMT, fibroblast-to-myofibroblast trans-differentiation and fibrogenesis in adenomyotic lesions. Thus, we provide the first piece of evidence strongly implicating the involvement of SCs in the pathogenesis of adenomyosis induced by EMID.

Perioperative Management of Patients with Rheumatic Disease: Cardiovascular Risks, Prevention of Infectious and Thromboembolic Complications, Other Conditions

In the first part we reviewed the issues of perioperative administration of steroids, disease-modifying antirheumatic drugs, biologics and nonsteroidal anti-inflammatory drugs. In this part we will discuss cardiovascular risks, prevention of infectious and thromboembolic complications and the impact of some structural alteration on the process of surgery and perioperative management.

A multinational online survey on the current perioperative practice for the management of patients with diabetes mellitus: a descriptive study

Background &amp; Objective: Diabetes mellitus is widely prevalent and significantly impacts the perioperative outcome. We aimed to assess the perioperative practice for managing diabetes mellitus patients and variation across different establishments.&#x0D; Methodology: A questionnaire-based online survey was conducted for the present cross-sectional, multinational study; data collection followed a snowball method and was conducted from November 2020 to January 2021. Responses were presented in absolute number and percentage scale, and response rates among the subgroups were analyzed using Fisher’s exact test; p &lt; 0.05 was considered significant.&#x0D; Results: Responses from 556 out of 637 from six South Asian Association for Regional Cooperation countries were analyzed. A considerable amount of practice variation was noted; variation increased as the invasiveness of surgery increased. Perioperative insulin administration strategy and case postponement based on blood sugar level differed between the teaching and non-teaching sectors and private and public sectors. However, a majority (64.8%) of the respondents did not favor postponing a case based on the glycosylated hemoglobin (HbA1c) level. Confusion and diverse opinions were present even for emergency cases, including postponement based on blood sugar.&#x0D; Conclusion: There is a wide variation in the perioperative practice for managing diabetes mellitus patients. The variation increases with the increasing invasiveness of surgery. Although there were similar practices between private versus public sectors and teaching versus non-teaching institutions, significant differences were noticed about case postponement, indicating that an authoritative guideline is the need of the hour.&#x0D; Key words: HbA1c level; Sugar, Cut-off; Sugar level; Anesthesia; Perioperative practice; Hyperglycemia&#x0D; Trial Registration: The study was an online survey and as per the clinical trial registry of India, it was not required to be registered.&#x0D; Citation: Karim HMR, Sharma A, Khan TH, Abayadeera AU, Alam MR. A multinational online survey on the current perioperative practice for the management of patients with diabetes mellitus: a descriptive study. Anaesth. pain intensive care 2022;26(1):382-390. DOI: 10.35975/apic.v26i3.1914&#x0D; Received: April 27, 2021; Reviewed: October 11, 2021; Accepted: December 16, 2021&#x0D;

Reduction of Postoperative Cognitive Deficits in Aged Mice by Chronic Intermittent Propofol

Postoperative cognitive dysfunction (POCD) can increase morbidity and mortality after surgery, especially in the elderly. Current evidence from both clinical/epidemiological studies and animal studies suggest that POCD is likely due to factors related to the surgery itself and at least not primarily due to the effects of general anesthetic agents. In contrast, propofol, the most commonly used intravenous general anesthetic agent which is acting mainly via GABAA receptors, has been shown to have neuroprotective effects by attenuating caspase activation, apoptosis, and mitochondrial dysfunction. We therefore set out to assess the effects of chronic intermittent propofol on postoperative cognitive deficits in aged mice. Abdominal surgery (exploratory laparotomy) under isoflurane anesthesia was performed in 21‐24 months‐old mice. Animals received either chronic intermittent propofol (75 mg/kg i.p.) or vehicle (IntralipidR) every 5th day throughout the experiment. The laparotomy was performed on day 17. Two days later, the mice were employed in the open field test. There was no difference in postoperative locomotor activity among groups (Surgery+Vehicle, Surgery+Propofol, No surgery+Vehicle, No surgery+Propofol). Then, cognitive functions were assessed using the Y maze, novel object recognition, contextual fear conditioning and Morris water maze tests. We found that laparotomy resulted in impaired learning and memory as determined in the behavioral test battery compared to no surgery controls. However, perioperative chronic intermittent propofol strongly attenuated the surgery‐induced memory impairments. Moreover, propofol per se improved the (likely age‐related) cognitive dysfunction in the no surgery controls. Our findings suggest that perioperative intermittent propofol administration might prevent or attenuate surgery‐induced cognitive dysfunction, and thus potentially reduce the liability for undesired long‐term outcomes. Thus, chronic intermittent administration of propofol may represent a novel therapeutic strategy with translational potential.

Impact of General Anesthesia and Antioxidants on Cognitive, Static and Locomotor Functions During Laparoscopic Cholecystectomy

Aim of the study: to reduce cognitive impairment during laparoscopic cholecystectomy by perioperative administration of drugs with antihypoxic and antioxidant effects under the control of stabilography. Materials and methods. We studied the effect of general anesthesia and antioxidants on cognitive, static and locomotor functions during laparoscopic cholecystectomy. We studied 90 patients with acute calculous cholecystitis randomized into three experimental groups (n=30, each group). The control group was composed of 24 healthy individuals. Group 1 patients received no antioxidants, group 2 patients received the combination antioxidant drug (sodium fumarate+sodium chloride+potassium chloride+magnesium chloride) in the post-operative period, and group 3 patients received methylethylpyridinol. The patient groups were comparable in sex, age and type of inflammatory and destructive process in the gallbladder. Surgical intervention was performed under endotracheal anesthesia. Premedication with atropine and promedol was given, and anesthesia induction was carried out with propofol, fentanyl and suxamethonium. Sevoflurane, fentanyl andcisatracurium were employed to maintain anesthesia, analgesia and myorelaxation, respectively. The patients were examined before surgery, 24 and 48 hours after surgery. In the groups of patients who received antioxidant therapy, blood sampling for hematological and biochemical examinations was performed 30 min after the administration of antioxidants. Stabilographic studies and MoCA test (Montreal Scale) were performed before antioxidant administration prior to surgery and after surgery, on days 2 and 3. Results. Neuropsychological testing revealed postoperative cognitive dysfunction on standard therapy which included impaired attention and concentration, executive function, memory, speech, visual constructional skills, abstract thinking, counting, and orientation (21 points on the MoCA scale versus 28–30 points for normal). We found that the pathogenetic factors of cognitive dysfunction included insufficient antioxidant protection, decreased TNF-α and elevated interleukin-18 levels along with an increased level of C-reactive protein in plasma, which manifested as activation of free-radical oxidation processes and reduced antioxidant system and performance of nonspecific resistance. Perioperative use of the combination antioxidant drug and methylethylpyridinol antioxidants reduced the frequency and severity of postoperative cognitive impairment in patients after laparoscopic cholecystectomy. Conclusion. The most important pathogenetic factors of cognitive dysfunction after laparoscopic cholecystectomy include activation of free-radical oxidation, reduction of antioxidant defense system performance and lack of nonspecific resistance factors. Adding the combination antioxidant drug or methylethylpyridinol to the standard therapy reduces the intensity of radical oxygen species generation, maintains the antioxidant potential, activates production and secretion of nonspecific resistance factors, preventing the development and reducing the severity of cognitive disorders in the perioperative period. Neuropsychological testing and stabilographic examination allow identifying the risk of cognitive disorders in patients after laparoscopic cholecystectomy and provide a rationale for the use of antioxidant therapy for their prevention.

Decreased Opioid Consumption in Bone Marrow Harvest Patients Using Quadratus Lumborum Blocks in a Standardized Protocol.

PurposeBone marrow harvesting is associated with significant postoperative pain that may have potential negative consequences for the patient and health care system. In the current absence of uniform guidelines, there exists considerable variability amongst providers with respect to perioperative analgesia, especially opioid administration. In this initiative, we explored the potential for preoperative bilateral quadratus lumborum blocks in combination with a standardized perioperative analgesic protocol to manage pain with the goal of reducing perioperative narcotic usage and thereby improving opioid stewardship.MethodsAdults who underwent bone marrow donation from 2018 to 2020 were included in this analysis (n = 32). The pre-implementation group (n = 19) was reviewed retrospectively while the implementation group (n = 13) was evaluated prospectively. Patient demographics, pain scores, and opioid consumption were evaluated.ResultsPatient characteristics were equivalent except for anesthesia type with an increased number of patients in the implementation group undergoing spinal anesthesia. The implementation group showed significantly reduced median intraoperative (20.0 mg vs. 0.0 mg; p < 0.001) and total opioid consumption (20.5 mg vs. 0.0 mg; p < 0.001). The number of patients who received any opioids decreased from 84.2% (16/19) before implementation to 23.1% (3/13) after implementation.ConclusionThis change in practice suggests that implementation of a standardized perioperative protocol, including bilateral quadratus lumborum blocks, for bone marrow harvest patients leads to reduced perioperative opioid administration without compromising immediate perioperative pain control.

Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma.

Simple SummaryHepatocellular carcinoma (HCC) is the most common primary hepatic malignancy, with increasing incidence over the past several decades. The majority of patients with HCC present with advanced unresectable disease, making treatment options with curative intent limited and survival outlooks dismal. Systemic therapy with sorafenib had been traditionally used, with marginal benefit. Immunotherapy, successfully used to treat other malignant tumors, has recently been shown to be safe and well tolerated and to have promising long-term outcomes in patients with advanced HCC. We herein review the outcomes of immune checkpoint inhibitors (ICI) from major clinical trials, summarize predictors of treatment response, and highlight adverse events related to ICI treatment.Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor. As a result of advanced disease being often present at diagnosis, only a small percentage of patients are amenable to curative-intent treatment options such as surgical resection and liver transplantation. Systemic therapy consisting of tyrosine kinase inhibitors such as sorafenib had been used for over a decade with limited efficacy. More recently, treatment with immune checkpoint inhibitors has revolutionized the treatment landscape of various malignant tumors. With this shifting paradigm, recent data have demonstrated encouraging outcomes among patients with HCC. In particular, several trials have investigated the safety and efficacy of various immune checkpoint inhibitors (ICI) either as monotherapy or in the form of combined treatments. We sought to provide an overview of recent clinical trials among patients with advanced HCC as well as to highlight predictors of response and immune-related adverse events and to review the evidence on perioperative administration of ICI in patients with resectable HCC.