Racial and Ethnic Differences in Postoperative Nausea and Vomiting Care.

BACKGROUND: Racial and ethnic differences in health care may result in significant morbidity. The objective of this study was to determine whether there was an association between a patient's race or ethnicity and the receipt of an antiemetic agent preoperatively, during surgery, and in the recovery room. METHODS: A single-institution retrospective study of adult patients (>18 years) who had undergone cancer-related operating room procedures under anesthesia between March 2016 and August 2021 was conducted. A multivariable logistic regression model was fitted to estimate the effects of covariates on antiemetic administration. RESULTS: Of the 60,595 patients included in the study, 3053 (5.0%) self-identified as Asian, 5376 (8.9%) as Black, 8431 (13.9%) as Hispanic or Latino, 42,533 (70.2%) as White, and 1202 (2.0%) as belonging to another racial or ethnic group. Multivariable analyses showed significant associations between a patient's race or ethnicity and the receipt of antiemetics in the preoperative holding area, operating room, and recovery room (all P < .001). In the preoperative holding area, White patients (8962 of 42,533 [21.1%]; odds ratio [OR], 1.188; 95% confidence interval [CI], 1.100-1.283; P < .001) had higher odds of receiving an antiemetic than Black patients (1006 of 5376 [18.7%]). Intraoperatively, the odds were significantly greater for Hispanic or Latino (7323 of 8431 [86.9%]; OR, 1.175; 95% CI, 1.065-1.297; P = .001) and patients who identified as belonging to another race (1078 of 1202 [89.7%]; OR, 1.582; 95% CI, 1.290-1.941; P < .001) than for Black patients (4468 of 5376 [83.1%]). In the recovery room, Asian (499 of 3053 [16.3%]; OR, 1.328; 95% CI: 1.127-1.561; P < .001), Hispanic or Latino (1335 of 8431 [15.8%]; OR, 1.208; 95% CI, 1.060-1.377; P < .005), and White patients (6533 of 42,533 [15.4%]; OR, 1.276; 95% CI, 1.140-1.427; P < .001) had significantly higher odds of receiving antiemetics than Black patients (646 of 5376 [12%]). CONCLUSIONS: This retrospective study suggests significant differences between the administrations of antiemetics to patients of different races or ethnicities, with Black patients often being less likely to receive an antiemetic than patients belonging to all other races or ethnicities.

Postoperative Complications Result in Poor Oncological Outcomes: What Is the Evidence?

The majority of patients with solid tumors undergo a curative resection of their tumor burden. However, the reported rate of postoperative complications varies widely, ranging from 10% to 70%. This narrative review aims to determine the impact of postoperative complications on recurrence and overall survival rates following elective cancer surgeries, thereby providing valuable insights into perioperative cancer care. A systematic electronic search of published studies and meta-analyses from January 2000 to August 2023 was conducted to examine the effect of postoperative complications on long-term survival after cancer surgeries. This comprehensive search identified fifty-one eligible studies and nine meta-analyses for review. Recurrence-free survival (RFS) and overall survival (OS) rates were extracted from the selected studies. Additionally, other oncological outcomes, such as recurrence and cancer-specific survival rates, were noted when RFS and OS were not reported as primary outcomes. Pooled hazard ratios and 95% confidence intervals were recorded from the meta-analyses, ensuring the robustness of the data. The analysis revealed that long-term cancer outcomes progressively worsen, from patients with no postoperative complications to those with minor postoperative complications (Clavien-Dindo grade ≤ II) and further to those with major postoperative complications (Clavien-Dindo grade III-IV), irrespective of cancer type. This study underscores the detrimental effect of postoperative complications on long-term oncological outcomes, particularly after thoracoabdominal surgeries. Importantly, we found a significant gap in the data regarding postoperative complications in surface and soft tissue surgical procedures, highlighting the need for further research in this area.

Intraoperative methadone administration for total mastectomy: A single center retrospective study.

BACKGROUND: Breast cancer is the most frequent type of cancer and the second leading cause of cancer-related mortality in women. Mastectomies remain a key component of the treatment of non-metastatic breast cancer, and strategies to treat acute postoperative pain, a complication affecting nearly all patients undergoing surgery, continues to be an important clinical challenge. This study aimed to determine the impact of intraoperative methadone administration compared to conventional short-acting opioids on pain-related perioperative outcomes in women undergoing a mastectomy. METHODS: This single-center retrospective study included adult women undergoing total mastectomy. The primary outcome of this study was postoperative pain intensity on day 1 after surgery. Secondary outcomes included perioperative opioid consumption, perioperative non-opioid analgesics use, duration of surgery and anesthesia, time to extubation, pain intensity in the postanesthesia care unit (PACU), anti-emetic use in PACU, and length of stay in hospital. We used the propensity score-based nearest matching with a 1:3 ratio to balance the patient baseline characteristics. RESULTS: 133 patients received methadone, and 2192 patients were treated with short-acting opioids. The analysis demonstrated that methadone was associated with significantly lower intraoperative and postoperative opioid consumption as measured by oral morphine equivalents and lower average pain intensity scores in the postanesthesia care unit. Moreover, methadone was also shown to reduce the use of non-opioid analgesia during surgery. CONCLUSION: Our study suggests that the unique pharmacological properties of methadone, including a short onset of action when given intravenously, long-acting pharmacokinetics, and multimodal effects, are associated with better acute pain management after a total mastectomy.

Tomivosertib reduces ectopic activity in dorsal root ganglion neurons from patients with radiculopathy.

Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in patients suffering from this largely untreated disease. While many intracellular signalling mechanisms have been examined in preclinical models that drive spontaneous activity, none have been tested directly on spontaneously active human nociceptors. Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we showed that inhibition of mitogen-activated protein kinase interacting kinase (MNK) with tomivosertib (eFT508, 25 nM) reversibly suppresses spontaneous activity in human sensory neurons that are likely nociceptors based on size and action potential characteristics associated with painful dermatomes within minutes of treatment. Tomivosertib treatment also decreased action potential amplitude and produced alterations in the magnitude of after hyperpolarizing currents, suggesting modification of Na+ and K+ channel activity as a consequence of drug treatment. Parallel to the effects on electrophysiology, eFT508 treatment led to a profound loss of eIF4E serine 209 phosphorylation in primary sensory neurons, a specific substrate of MNK, within 2 min of drug treatment. Our results create a compelling case for the future testing of MNK inhibitors in clinical trials for neuropathic pain.

Opioids and Cancer: Current Understanding and Clinical Considerations.

Pain is one of the most common symptoms in patients with cancer. Pain not only negatively affects the quality of life of patients with cancer, but it has also been associated with reduced survival. Pain management is therefore a critical component of cancer care. Prescription opioids remain the first-line approach for the management of moderate-to-severe pain associated with cancer. However, there has been increasing interest in understanding whether these analgesics could impact cancer progression. Furthermore, epidemiological data link a possible association between prescription opioid usage and cancer development. Until more robust evidence is available, patients with cancer with moderate-to-severe pain may receive opioids to decrease suffering. However, future studies should be conducted to evaluate the role of opioids and opioid receptors in specific cancers.

Markers of Tissue Deterioration and Pain on Earth and in Space.

Purpose: Pain is an understudied physiological effect of spaceflight. Changes in inflammatory and tissue degradation markers are often associated with painful conditions. Our aim was to evaluate the changes in markers associated with tissue deterioration after a short-term spaceflight. Patients and Methods: Plasma levels of markers for systemic inflammation and tissue degeneration markers were assessed in two astronauts before and within 24 h after the 17-day Axiom Space AX-1 mission. Results: After the spaceflight, C-reactive protein (CRP) was reduced in both astronauts, while INFγ, GM-CSF, TNFα, BDNF, and all measured interleukins were consistently increased. Chemokines demonstrated variable changes, with consistent positive changes in CCL3, 4, 8, 22 and CXCL8, 9, 10, and consistent negative change in CCL8. Markers associated with tissue degradation and bone turnover demonstrated consistent increases in MMP1, MMP13, NTX and OPG, and consistent decreases in MMP3 and MMP9. Conclusion: Spaceflight induced changes in the markers of systemic inflammation, tissue deterioration, and bone resorption in two astronauts after a short, 17-day, which were often consistent with those observed in painful conditions on Earth. However, some differences, such as a consistent decrease in CRP, were noted. All records for the effect of space travel on human health are critical for improving our understanding of the effect of this unique environment on humans.

Prehabilitation in Adults Undergoing Cancer Surgery: A Comprehensive Review on Rationale, Methodology, and Measures of Effectiveness.

Cancer surgery places a significant burden on a patients' functional status and quality of life. In addition, cancer surgery is fraught with postoperative complications, themselves influenced by a patient's functional status. Prehabilitation is a unimodal or multimodal strategy that aims to increase a patient's functional capacity to reduce postoperative complications and improve postoperative recovery and quality of life. In most cases, it involves exercise, nutrition, and anxiety-reducing interventions. The impact of prehabilitation has been explored in several types of cancer surgery, most commonly colorectal and thoracic. Overall, the existing evidence suggests prehabilitation improves physiological outcomes (e.g., lean body mass, maximal oxygen consumption) as well as clinical outcomes (e.g., postoperative complications, quality of life). Notably, the benefit of prehabilitation is additional to that of enhanced recovery after surgery (ERAS) programs. While safe, prehabilitation programs require multidisciplinary coordination preoperatively. Despite the existence of numerous systematic reviews and meta-analyses, the certainty of evidence demonstrating the efficacy and safety of prehabilitation is low to moderate, principally due to significant methodological heterogeneity and small sample sizes. There is a need for more large-scale multicenter randomized controlled trials to draw strong clinical recommendations.

Use of a Combination Lavender/Peppermint Aromatherapy Patch During Port Catheter Placement Under Monitored Anesthesia Care Does Not Reduce Time to Discharge Readiness: A Randomized Controlled Trial.

Background: Intraoperative anxiety is a common problem when Monitored Anesthesia Care (MAC) is used instead of general anesthesia during minor surgical procedures such as port catheter placement. Nonpharmacological anxiolytics such as aromatherapy have been studied for their effects on preoperative anxiety, but no placebo-controlled study of aromatherapy during surgeries under MAC has yet been performed. Methods: After IRB approval, 70 patients were randomized 1:1 to receive either a lavender/peppermint aromatherapy patch (Elequil Aromatabs®; Beekley Corporation) or a matching placebo patch. The primary outcome, time to readiness for discharge from postoperative acute care units (PACU; min), was assessed every 15 min until a modified postanesthesia recovery score for ambulatory patients (PARSAP) score of 18 or higher was reached. In the preoperative holding area, the assigned patch/placebo was activated and affixed to a folded towel placed aside the subject's head, contralateral to the side of the planned surgery. The towel and patch/placebo were discarded when the subject left the operating room (OR). Results: No difference was found between the treatment and placebo groups on the primary outcome of time to discharge readiness (mean [standard deviation, SD]: 82 [15] vs. 89 [21] min, respectively, p = 0.131). No difference was found between the treatment and placebo groups on the secondary outcomes of intraoperative midazolam dose, intraoperative opioid dose, intraoperative ondansetron dose, or intraoperative promethazine dose. No difference was found between the treatment and placebo groups in the proportion of subjects requiring rescue postoperative nausea and vomiting (PONV) medication in the PACU or the proportion of subjects requiring opioids in the PACU. No difference was found between the treatment and placebo groups in pain intensity in PACU, average PONV score in PACU, or patient satisfaction in PACU. PACU patient satisfaction was high for both the patch and placebo groups (35/35 [100%] vs. 32/34 [94%] "very satisfied," p = 0.239). Conclusions: Aromatherapy treatment is not indicated intraoperatively to reduce anxiety or the use of antiemetics in patients requiring Port catheter placement. Trial registration: Clinicaltrials.gov, identifier: NCT05328973.

Lost in Translation: Failure of Preclinical Studies to Accurately Predict the Effect of Regional Analgesia on Cancer Recurrence.

The major goal of translational research is to evaluate the efficacy and effectiveness of treatments and interventions that have emerged from exhaustive preclinical evidence. In 2007, a major clinical trial was started to investigate the impact of paravertebral analgesia on breast cancer recurrence. The trial was based on preclinical evidence demonstrating that spinal anesthesia suppressed metastatic dissemination by inhibiting surgical stress, boosting the immunological response, avoiding volatile anesthetics, and reducing opioid use. However, that trial and three more recent randomized trials with a total of 4,770 patients demonstrate that regional analgesia does not improve survival outcomes after breast, lung, and abdominal cancers. An obvious question is why there was an almost complete disconnect between the copious preclinical investigations suggesting benefit and robust clinical trials showing no benefit? The answer is complex but may result from preclinical research being mechanistically driven and based on reductionist models. Both basic scientists and clinical investigators underestimated the limitations of various preclinical models, leading to the apparently incorrect hypothesis that regional anesthesia reduces cancer recurrence. This article reviews factors that contributed to the discordance between the laboratory science, suggesting that regional analgesia might reduce cancer recurrence and clinical trials showing that it does not-and what can be learned from the disconnect.

Pain Experience and Sensory Changes in Astronauts During and After Short-Lasting Commercial Spaceflight: A Proof-of-Concept Study.

Space travel has been associated with musculoskeletal pain, yet little is known about the nociceptive changes and pain experience during spaceflight. This preliminary study aims to investigate the pain experience and sensory alterations in astronauts following a 17-day mission to the International Space Station (ISS) on Axiom Space's AX-1 commercial space flight. Two participants were enrolled, and data were collected pre-flight, in-flight, post-flight, and three-month post-flight. Validated pain questionnaires assessed anxiety, catastrophizing, impact on physical and mental health, disability, and overall pain experience. Qualitative interviews were conducted post-landing and conditioned pain modulation (CPM) and quantitative sensory testing (QST) were performed. Both astronauts reported musculoskeletal pain during and after the flight, which was managed with anti-inflammatories and stretching techniques. Pain levels returned to baseline after three months. Pain questionnaires revealed heightened pain experiences in-flight and immediately post-flight, although their adequacy in assessing pain in space is uncertain. Qualitative interviews allowed astronauts to describe their pain experiences during the flight. Sensory changes included increased mechanical touch detection thresholds, temporal pain summation, heat pain thresholds, and differences in conditioned pain modulation post-flight. This preliminary study suggested that spaceflight may affect various aspects of sensory perception and regulation in astronauts, albeit in a variable manner. More data are needed to gain insight of on gain and loss of sensory functions during space missions. Further investigation into the multifactorial stressors affecting the somatosensory system during space travel could contribute to advancements in space and pain medicine.

Enhanced recovery protocols for ambulatory surgery.

INTRODUCTION: In the United States, ambulatory surgeries account for up to 87% of all surgical procedures. (1) It was estimated that 19.2 million ambulatory surgeries were performed in 2018 (https://www.hcup-us.ahrq.gov/reports/statbriefs/sb287-Ambulatory-Surgery-Overview-2019.pdf). Cataract procedures and musculoskeletal surgeries are the most common surgical interventions performed in ambulatory centers. However, more complex surgical interventions, such as sleeve gastrectomies, oncological, and spine surgeries, and even arthroplasties are routinely performed as day cases or in a model of an ambulatory extended recovery. (2-5) The ambulatory surgery centers industry has grown since 2017 by 1.1% per year and reached a market size of $31.2 billion. According to the Ambulatory Surgery Center Association, there is a potential to save $57.6 billion in Medicare costs over the next decade (https://www.ibisworld.com/industry-statistics/market-size/ambulatory-surgery-centers-united-states/). These data suggest an expected rise in the volume of ambulatory (same day) or extended ambulatory (23 h) surgeries in coming years. Similar increases are also observed in other countries. For example, 75% of elective surgeries are performed as same-day surgery in the United Kingdom. (6) To reduce costs and improve the quality of care after those more complex procedures, ambulatory surgery centers have started implementing patient-centered, high-quality, value-based practices. To achieve those goals, Enhanced Recovery After Surgery (ERAS) protocols have been implemented to reduce the length of stay, decrease costs, increase patients' satisfaction, and transform clinical practices. The ERAS fundamentals for ambulatory surgery are based on five pillars, including (1) preoperative patient counseling, education, and optimization; (2) multimodal and opioid-sparing analgesia; (3) nausea and vomiting, wound infection, and venous thromboembolism prophylaxis; (4) maintenance of euvolemia; and (5) encouragement of early mobility. Those pillars rely on interdisciplinary teamwork led by anesthesiologists, surgery-specific workgroups, and safety culture. (2) Research shows that a team of ambulatory anesthesiologists is crucial in improving postoperative nausea and vomiting (PONV) and pain control. (7) This review will summarize the current evidence on the elements and clinical importance of implementing ERAS protocol for ambulatory surgery.

Race, Ethnicity, and Sustained Opioid Use After Major Abdominal Surgery for Cancer.

Purpose: Sustained opioid use is a well-known complication after surgery. Our objective was to determine whether there is any association between a patient's race or ethnicity and the sustained use of opioids in the year following surgery. Opioid use over the initial 3, 6, and 12 postoperative months was categorized as "sustained early", persistent, and chronic, respectively. Patients and Methods: Single-institution retrospective study of adults (≥18 years) who had undergone open abdominal surgery for cancer. Multivariable logistic regression was used to evaluate the association between race/ethnicity and opioid use. Results: Of the 3523 patients included in the study, 2543 (72.2%) were non-Hispanic (NH) White, 476 (13.5%) were Hispanic or Latino, 262 (7.4%) were NH-Black, 186 (5.3%) were Asian, and 56 (1.6%) belonged to other racial or ethnic groups. The overall rates of sustained early, persistent, and chronic opioid use were 15.9%, 7.1%, and 2.6%, respectively. In the multivariable analysis, patient race/ethnicity was associated with sustained early postoperative opioid use (p-value=0.037), with Hispanics/Latinos having significantly higher odds than NH-Whites (OR = 1.382 [95% CI: 1.057-1.808]; p = 0.018). However, neither persistent nor chronic opioid use was associated with race/ethnicity (p = 0.697 and p = 0.443, respectively). Conclusion: In this retrospective study of adults who had undergone open abdominal surgery, patient race/ethnicity was not consistently associated with the development of sustained opioid use over the first 12 postoperative months.

Antiemetic prophylaxis with droperidol in morphine-based intravenous patient-controlled analgesia: a propensity score matched cohort study.

BACKGROUND: There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA. METHODS: Patients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: After matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35-0.67, p < 0.0001). The antiemetic effect of droperidol was significant within 36 h after surgery and attenuated thereafter. Droperidol was significantly associated with a lower risk of antiemetic uses (aOR: 0.58, 95% CI: 0.41-0.80, p = 0.0011). The rate of unintentional sedation was comparable between the patients with (9.1%) and without (7.8%; p = 0.4481) the addition of droperidol. Postoperative opioid consumption and numeric rating scale acute pain scores were similar between groups. CONCLUSIONS: The addition of droperidol to IV-PCA reduced the risk of PONV without increasing opiate consumption or influencing the level of sedation. However, additional prophylactic therapies are needed to prevent late-onset PONV.

METTL3-mediated N6-methyladenosine exacerbates ferroptosis via m6A-IGF2BP2-dependent mitochondrial metabolic reprogramming in sepsis-induced acute lung injury.

Neutrophil extracellular traps (NETs), released by polymorphonuclear neutrophils (PMNs), exert a robust antimicrobial function in infectious diseases such as sepsis. NETs also contribute to the pathogenesis and exacerbation of sepsis. Although the lung is highly vulnerable to infections, few studies have explored the role of NETs in sepsis-induced acute lung injury (SI-ALI). We demonstrate that NETs induce SI-ALI via enhanced ferroptosis in alveolar epithelial cells. Our findings reveal that the excessive release of NETs in patients and mice with SI-ALI is accompanied by upregulation of ferroptosis depending on METTL3-induced m6A modification of hypoxia-inducible factor-1α (HIF-1α) and subsequent mitochondrial metabolic reprogramming. In addition to conducting METTL3 overexpression and knockdown experiments in vitro, we also investigated the impact of ferroptosis on SI-ALI caused by NETs in a caecum ligation and puncture (CLP)-induced SI-ALI model using METTL3 condition knockout (CKO) mice and wild-type mice. Our results indicate the crucial role of NETs in the progression of SI-ALI via NET-activated METTL3 m6A-IGF2BP2-dependent m6A modification of HIF-1α, which further contributes to metabolic reprogramming and ferroptosis in alveolar epithelial cells.

Effect of neoadjuvant chemotherapy on intraoperative core temperature in patients with breast cancer: a retrospective cohort study.

Background: Clinical evidence suggests that chemotherapeutic agents are associated with neuropathy and peripheral autonomic dysfunction. However, the possible effects of neoadjuvant chemotherapy on intraoperative temperature remain poorly characterised. Methods: We evaluated patients who underwent a mastectomy for breast cancer between April 2016 and July 2020. Propensity scores were used to match patients who received neoadjuvant chemotherapy with those who did not, and intraoperative core temperature patterns were analysed in the matched cohort. The independent associations between vasopressor use and heart rate during general anaesthesia in the matched cohort were also analysed. Results: Data from 1764 patients were analysed (882 patients in each group). Both groups presented a similar pattern of heat redistribution and subsequent rewarming; however, the neoadjuvant chemotherapy group did not reach the same intraoperative plateau temperature as the group that did not receive prior chemotherapy, with differences of up to 0.4°C (95% confidence interval: 0.11-0.63°C; P=0.005). In a subgroup analysis, neuropathy in patients who received neoadjuvant chemotherapy was associated with increased use of vasopressors and higher heart rate. Conclusions: In patients with breast cancer, neoadjuvant chemotherapy is associated with lower plateau core temperatures, increased vasopressor use, and higher heart rates during general anaesthesia, which is more severe in the presence of neuropathy.

Incidence of acute kidney injury after noncardiac surgery in patients receiving intraoperative dexmedetomidine: a retrospective study.

Background: Postoperative acute kidney injury (AKI) is a common complication and is associated with increased hospital length of stay and 30 day all-cause mortality. Unfortunately, we have neither a defined strategy to prevent AKI nor an effective treatment. In vitro, animal, and human studies have suggested that dexmedetomidine may have a renoprotective effect. We conducted a retrospective cohort study to evaluate if intraoperative dexmedetomidine was associated with a reduced incidence of AKI. Methods: We collected data from 6625 patients who underwent major non-cardiothoracic cancer surgery. Before and after propensity score matching, we compared the incidence of postoperative AKI in patients who received intraoperative dexmedetomidine and those who did not. AKI was defined according to the Kidney Disease Improving Global Outcomes (creatinine alone values) criteria and calculated for postoperative Days 1, 2, and 3. Results: Twenty per cent (n=1301) of the patients received dexmedetomidine. The mean [standard deviation] administered dose was 78 [49.4] mcg. Patients treated with dexmedetomidine were matched to those who did not receive the drug. Patients receiving dexmedetomidine had a longer anaesthesia duration than the non-dexmedetomidine group. The incidence of AKI was not significantly different between the groups (dexmedetomidine 8% vs no dexmedetomidine 7%; P=0.333). The 30 day rates of infection, cardiovascular complications, or reoperation attributable to bleeding were higher in patients treated with dexmedetomidine. The 30 day mortality rate was not statistically different between the groups. Conclusions: The administration of dexmedetomidine during major non-cardiothoracic cancer surgery is not associated with a reduction in AKI within 72 h after surgery.