Risk factors for persistent pain after breast cancer surgery: a multicentre prospective cohort study.

Identifying factors associated with persistent pain after breast cancer surgery may facilitate risk stratification and individualised management. Single-population studies have limited generalisability as socio-economic and genetic factors contribute to persistent pain development. Therefore, this prospective multicentre cohort study aimed to develop a predictive model from a sample of Asian and American women. We enrolled women undergoing elective breast cancer surgery at KK Women's and Children's Hospital and Duke University Medical Center. Pre-operative patient and clinical characteristics and EQ-5D-3L health status were recorded. Pain catastrophising scale; central sensitisation inventory; coping strategies questionnaire-revised; brief symptom inventory-18; perceived stress scale; mechanical temporal summation; and pressure-pain threshold assessments were performed. Persistent pain was defined as pain score ≥ 3 or pain affecting activities of daily living 4 months after surgery. Univariate associations were generated using generalised estimating equations. Enrolment site was forced into the multivariable model, and risk factors with p < 0.2 in univariate analyses were considered for backwards selection. Of 210 patients, 135 (64.3%) developed persistent pain. The multivariable model attained AUC = 0.807, with five independent associations: age (OR 0.85 95%CI 0.74-0.98 per 5 years); diabetes (OR 4.68, 95%CI 1.03-21.22); pre-operative pain score at sites other than the breast (OR 1.48, 95%CI 1.11-1.96); previous mastitis (OR 4.90, 95%CI 1.31-18.34); and perceived stress scale (OR 1.35, 95%CI 1.01-1.80 per 5 points), after adjusting for: enrolment site; pre-operative pain score at the breast; pre-operative overall pain score at rest; postoperative non-steroidal anti-inflammatory drug use; and pain catastrophising scale. Future research should validate this model and evaluate pre-emptive interventions to reduce persistent pain risk.

Obesity in women: anaesthetic implications for peri-operative and peripartum management.

The prevalence, healthcare and socio-economic impact of obesity (defined as having a body mass index of ≥ 30 kg.m-2 ) are disproportionately higher in women than men. A combination of biological and social factors, including the adaptation of energy homeostasis to the increased demands of pregnancy and lactation and poor access to healthy foods or exercise facilities, contribute to the increasing prevalence of obesity in women. Obesity-related physiological changes stem from mass loading and increased metabolism of adipose tissue, as well as secretion of bioactive substances from adipocytes leading to chronic low-grade inflammation. As a result, obesity is associated with increased risks of: infertility; malignancy; sleep-disordered breathing; cardiovascular disease; diabetes; and thromboembolism. Hence, obese women are at markedly increased risk of peri-operative morbidity and mortality and require comprehensive evaluation and targeted comorbidity optimisation by a multidisciplinary team. In addition to routine obstetric challenges, pregnancy in women with obesity further exacerbates the above risks, making multidisciplinary management starting at pre-conception even more important. Weight loss, lifestyle management and optimisation of comorbidity are the cornerstone of reducing obesity-related risks. The anaesthetist plays a vital role within the multidisciplinary team by emphasising weight loss as part of pre-operative comorbidity optimisation, formulation of individualised peri-operative management plans, supervising postoperative care in the high dependency or intensive care settings and providing safe labour analgesia and careful peripartum management for obese parturients.

Supplemental peri-operative intravenous crystalloids for postoperative nausea and vomiting: an abridged Cochrane systematic review.

We conducted a Cochrane systematic review on the effectiveness of supplemental intravenous crystalloid administration in preventing postoperative nausea and vomiting. We included randomised controlled trials of patients undergoing surgery under general anaesthesia and given supplemental peri-operative intravenous crystalloid. Our primary outcomes were the risk of postoperative nausea and the risk of postoperative vomiting. We assessed the risk of bias for each included study and applied the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework for the certainty of evidence. We included 41 studies. We found that the intervention probably reduces the overall risk of postoperative nausea, the risk ratio (95%CI) being 0.62 (0.51-0.75) (I2  = 57%, p < 0.00001, 18 studies; 1766 participants; moderate-certainty evidence). It also probably reduces the risk of postoperative nausea within 6 h of surgery, with a risk ratio (95%CI) of 0.67 (0.58 to 0.78) (I2  = 9%, p < 0.00001, 20 studies; 2310 participants; moderate-certainty evidence) and by around 24 h, the risk ratio (95%CI) being 0.47 (0.32-0.69) (I2  = 38%, p = 0.0001, 17 studies; 1682 participants; moderate-certainty evidence). Supplemental intravenous crystalloid probably also reduces the overall risk of postoperative vomiting, with a risk ratio (95%CI) of 0.50 (0.40-0.63) (I2  = 31%, p < 0.00001, 20 studies; 1970 participants; moderate-certainty evidence). The beneficial effect on vomiting was seen both within 6 h and by around 24 h postoperatively.

High-dose versus low-dose local anaesthetic for transversus abdominis plane block post-Caesarean delivery analgesia: a meta-analysis.

BACKGROUND: The optimal local-anaesthetic (LA) dose for transversus-abdominis-plane (TAP) block is unclear. In this meta-analysis, we aimed to determine whether TAP blocks for Caesarean delivery (CD) with low-dose (LD) LA demonstrated non-inferiority in terms of analgesic efficacy, compared with high-dose (HD) LA. METHODS: A literature search was performed for randomised controlled trials examining the analgesic efficacy of TAP blocks vs control after CD. The different dosing used in these studies was classified as HD or LD (bupivacaine equivalents >50 or ≤50 mg per block side, respectively). The pooled results of each dose group vs control were indirectly compared using the Q test. The primary outcome was 24 h opioid consumption. Secondary outcomes included 6 and 24 h postoperative pain scores, time to first analgesia, 6 h opioid consumption, opioid-related side-effects, and maternal satisfaction. RESULTS: Fourteen studies consisting of 770 women (389 TAP and 381 control) were included. Compared with controls, the 24 h opioid consumption (milligram morphine equivalents) was lower in HD [mean difference (MD) 95% confidence interval (CI) -22.41 (-38.56, -6.26); P=0.007; I2=93%] and LD [MD 95% CI -16.29 (-29.74, -2.84); P=0.02; I2=98%] TAP groups. However, no differences were demonstrated between the HD and LD groups (P=0.57). There were also no differences between the HD and LD groups for the 6 h opioid consumption, time to first analgesia, 6 and 24 h pain scores, postoperative nausea and vomiting, pruritus, and maternal satisfaction. CONCLUSIONS: Low-dose TAP blocks for Caesarean delivery provide analgesia and opioid-sparing effects comparable with the high-dose blocks. This suggests that lower doses can be used to reduce local anaesthetic toxicity risk without compromising the analgesic efficacy.

The impact of neuraxial clonidine on postoperative analgesia and perioperative adverse effects in women having elective Caesarean section-a systematic review and meta-analysis.

Neuraxial clonidine improves postoperative analgesia in the general surgical population. The efficacy and safety of neuraxial clonidine as a postoperative analgesic adjunct in the Caesarean section population still remains unclear. This systematic review and meta-analysis aims to evaluate the effect of perioperative neuraxial clonidine on postoperative analgesia in women having Caesarean section under neuraxial anaesthesia. We included randomized controlled trials comparing the analgesic efficacy of the perioperative administration of neuraxial clonidine alone or in combination with a local anaesthetic and/or opioids in women having elective Caesarean section under neuraxial anaesthesia when compared with placebo. PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE were searched until February 2017. Eighteen studies were included in the meta-analysis. Neuraxial clonidine reduced 24 h morphine consumption [mean difference (MD): -7.2 mg; 95% confidence interval (CI): -11.4, -3.0 mg; seven studies] and prolonged time to first analgesic request (MD: 135 min; 95% CI: 102, 168 min; 16 studies) when compared with the control group. Neuraxial clonidine increased intraoperative hypotension [odds ratio (OR): 2.849; 95% CI: 1.363, 5.957], intraoperative sedation (OR: 2.355; 95% CI: 1.016, 5.459), but reduced the need for intraoperative analgesic supplementation (OR: 0.224; 95% CI: 0.076, 0.663). The effect of clonidine on intraoperative bradycardia, intraoperative and postoperative nausea and vomiting, postoperative sedation, and pruritus were inconclusive. Neuraxial clonidine did not negatively impact neonatal umbilical artery pH or Apgar scores. This review demonstrates that neuraxial clonidine enhances postoperative analgesia in women having Caesarean section with neuraxial anaesthesia, but this has to be balanced against increased maternal adverse effects.

The effect of anti-emetic doses of dexamethasone on postoperative blood glucose levels in non-diabetic and diabetic patients: a prospective randomised controlled study.

There are few data regarding postoperative hyperglycaemia in non-diabetic compared with diabetic patients following postoperative nausea and vomiting prophylaxis with dexamethasone. Eighty-five non-diabetic patients and patients with type-2 diabetes were randomly allocated to receive intravenous dexamethasone (8 mg) or ondansetron (4 mg). Blood glucose levels were measured at baseline and then 2, 4 and 24 h following induction of anaesthesia. In non-diabetic patients, the mean (SD) maximum blood glucose was higher in those who received dexamethasone compared with ondansetron (9.1 (2.2) mmol.l(-1) vs. 7.8 (1.4) mmol.l(-1) , p = 0.04). In diabetic patients, the mean (SD) maximum blood glucose was also higher in those who received dexamethasone compared with ondansetron (14.0 (2.5) mmol.l(-1) vs. 10.7 (2.4) mmol.l(-1) , p < 0.01). Multivariate analysis demonstrated that dexamethasone administration was a significant predictor of maximum postoperative blood glucose increase (p < 0.01) after adjusting for potential confounders. There was no interaction between baseline blood glucose level, or presence or absence of diabetes, and dexamethasone administration. We conclude that dexamethasone increases postoperative blood glucose levels in both non-diabetics and diabetics.

The Effect of patient warming during Caesarean delivery on maternal and neonatal outcomes: a meta-analysis.

BACKGROUND: Perioperative warming is recommended for surgery under anaesthesia, however its role during Caesarean delivery remains unclear. This meta-analysis aimed to determine the efficacy of active warming on outcomes after elective Caesarean delivery. METHODS: We searched databases for randomized controlled trials utilizing forced air warming or warmed fluid within 30 min of neuraxial anaesthesia placement. Primary outcome was maximum temperature change. Secondary outcomes included maternal (end of surgery temperature, shivering, thermal comfort, hypothermia) and neonatal (temperature, umbilical cord pH and Apgar scores) outcomes. Standardized mean difference/mean difference/risk ratio (SMD/MD/RR) and 95% confidence interval (CI) were calculated using random effects modelling (CMA, version 2, 2005). RESULTS: 13 studies met our criteria and 789 patients (416 warmed and 373 controls) were analysed for the primary outcome. Warming reduced temperature change (SMD -1.27°C [-1.86, -0.69]; P=0.00002); resulted in higher end of surgery temperatures (MD 0.43 °C [0.27, 0.59]; P<0.00001); was associated with less shivering (RR 0.58 [0.43, 0.79]; P=0.0004); improved thermal comfort (SMD 0.90 [0.36, 1.45]; P=0.001), and decreased hypothermia (RR 0.66 [0.50, 0.87]; P=0.003). Umbilical artery pH was higher in the warmed group (MD 0.02 [0, 0.05]; P=0.04). Egger's test (P=0.001) and contour-enhanced funnel plot suggest a risk of publication bias for the primary outcome of temperature change. CONCLUSIONS: Active warming for elective Caesarean delivery decreases perioperative temperature reduction and the incidence of hypothermia and shivering. These findings suggest that forced air warming or warmed fluid should be used for elective Caesarean delivery.

Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis.

We performed this systematic review to assess the analgesic efficacy of perioperative pregabalin. Subgroup analyses and meta-regression were performed to assess the impact of individual dose and frequency of pregabalin administration on analgesic efficacy. We included 55 studies. When all doses and administration regimens were combined, pregabalin was associated with a significant reduction in pain scores at rest and during movement and opioid consumption at 24 h compared with placebo {mean difference [95% confidence interval (CI)]=-0.38 (-0.57, -0.20), -0.47 (-0.76, -0.18), and -8.27 mg morphine equivalents (-10.08, -6.47), respectively}. Patients receiving pregabalin had less postoperative nausea and vomiting and pruritus compared with placebo [relative risk (RR) (95% CI)=0.62 (0.48, 0.80) and 0.49 (0.34, 0.70), respectively]. Sedation, dizziness, and visual disturbance were more common with pregabalin compared with placebo [RR (95% CI)=1.46 (1.08, 1.98), 1.33 (1.07, 1.64), and 3.52 (2.05, 6.04), respectively]. All doses of pregabalin tested (≤75, 100-150, and 300 mg) resulted in opioid sparing at 24 h after surgery. There were no significant differences in acute pain outcomes with pregabalin 100-300 mg between single preoperative dosing regimens and those including additional doses repeated after surgery. Data were insufficient to reach conclusions regarding persistent pain, but limited data available from two studies suggested that pregabalin might be effective for the reduction of neuropathic pain. In conclusion, this review suggests that pregabalin improves postoperative analgesia compared with placebo at the expense of increased sedation and visual disturbances.

Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis.

BACKGROUND: The analgesic efficacy and adverse effects of a single perioperative dose of dexamethasone are unclear. We performed a systematic review to evaluate the impact of a single i.v. dose of dexamethasone on postoperative pain and explore adverse events associated with this treatment. METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Register were searched for randomized, controlled studies that compared dexamethasone vs placebo or an antiemetic in adult patients undergoing general anaesthesia and reported pain outcomes. RESULTS: Forty-five studies involving 5796 patients receiving dexamethasone 1.25-20 mg were included. Patients receiving dexamethasone had lower pain scores at 2 h {mean difference (MD) -0.49 [95% confidence interval (CI): -0.83, -0.15]} and 24 h [MD -0.48 (95% CI: -0.62, -0.35)] after surgery. Dexamethasone-treated patients used less opioids at 2 h [MD -0.87 mg morphine equivalents (95% CI: -1.40 to -0.33)] and 24 h [MD -2.33 mg morphine equivalents (95% CI: -4.39, -0.26)], required less rescue analgesia for intolerable pain [relative risk 0.80 (95% CI: 0.69, 0.93)], had longer time to first dose of analgesic [MD 12.06 min (95% CI: 0.80, 23.32)], and shorter stays in the post-anaesthesia care unit [MD -5.32 min (95% CI: -10.49 to -0.15)]. There was no dose-response with regard to the opioid-sparing effect. There was no increase in infection or delayed wound healing with dexamethasone, but blood glucose levels were higher at 24 h [MD 0.39 mmol litre(-1) (95% CI: 0.04, 0.74)]. CONCLUSIONS: A single i.v. perioperative dose of dexamethasone had small but statistically significant analgesic benefits.

Role of cosyntropin in the management of postpartum post-dural puncture headache: a two-center retrospective cohort study.

BACKGROUND: Research suggests that postpartum post-dural puncture headache (PDPH) might be prevented or treated by administering intravenous cosyntropin. METHODS: In this retrospective cohort study, we questioned whether prophylactic (1 mg) and therapeutic (7 µg/kg) intravenous cosyntropin following unintentional dural puncture (UDP) was effective in decreasing the incidence of PDPH and therapeutic epidural blood patch (EBP) after birth. Two tertiary-care American university hospitals collected data from November 1999 to May 2017. Two hundred and fifty-three postpartum patients who experienced an UDP were analyzed. In one institution 32 patients were exposed to and 32 patients were not given prophylactic cosyntropin; in the other institution, once PDPH developed, 36 patients were given and 153 patients were not given therapeutic cosyntropin. The primary outcome for the prophylactic cosyntropin analysis was the incidence of PDPH and for the therapeutic cosyntropin analysis in exposed vs. unexposed patients, the receipt of an EBP. The secondary outcome for the prophylactic cosyntropin groups was the receipt of an EBP. RESULTS: In the prophylactic cosyntropin analysis no significant difference was found in the risk of PDPH between those exposed to cosyntropin (19/32, 59%) and unexposed patients (17/32, 53%; odds ratio (OR) 1.37, 95% CI 0.48 to 3.98, P = 0.56), or in the incidence of EBP between exposed (12/32, 38%) and unexposed patients (6/32, 19%; OR 2.6, 95% CI 0.83 to 8.13, P = 0.095). In the therapeutic cosyntropin analysis, in patients exposed to cosyntropin the incidence of EBP was significantly higher (20/36, 56% vs. 43/153, 28%; OR 3.20, 95% CI 1.52 to 6.74, P = 0.002). CONCLUSIONS: Our data show no benefits from the use of cosyntropin for preventing or treating postpartum PDPH.

Metoclopramide for nausea and vomiting prophylaxis during and after Caesarean delivery: a systematic review and meta-analysis.

Nausea and vomiting occur commonly during and after Caesarean delivery (CD) performed under neuraxial anaesthesia. Metoclopramide is a prokinetic agent reported to be safe in parturients. This meta-analysis assesses the efficacy of metoclopramide for prophylaxis against intra- and postoperative nausea and vomiting (IONV and PONV) in parturients undergoing CD under neuraxial anaesthesia. We performed a literature search of MEDLINE (1966-2011), Cochrane Central Register of Controlled Trials, EMBASE (1947-2011), Google scholar, and CINAHL for randomized controlled trials which compared metoclopramide with placebo in women having CD under neuraxial anaesthesia. Eleven studies with 702 patients were included in the analysis. Administration of metoclopramide (10 mg) resulted in a significant reduction in the incidence of ION and IOV when given before block placement [relative risk (RR) (95% confidence interval, 95% CI)=0.27 (0.16, 0.45) and 0.14 (0.03, 0.56), respectively] or after delivery [RR (95% CI)=0.38 (0.20, 0.75) and 0.34 (0.18, 0.66), respectively]. The incidence of early (0-3 or 0-4 h) PON and POV [RR (95% CI)=0.47 (0.26, 0.87) and 0.45 (0.21, 0.93), respectively] and overall (0-24 or 3-24 h) PON (RR 0.69; 95% CI 0.52, 0.92) were also reduced with metoclopramide. Extra-pyramidal side-effects were not reported in any patient. In conclusion, this review suggests that metoclopramide is effective and safe for IONV and PONV prophylaxis in this patient population. Given the quality of the studies and the infrequent use of neuraxial opioids, these results should be interpreted with caution in current practice and further studies are needed to confirm those findings.

Intrathecal bupivacaine versus chloroprocaine for transvaginal cervical cerclage placement: a retrospective cohort study.

BACKGROUND: Bupivacaine is commonly used in spinal anesthesia for cervical cerclage placement, but its long duration of action can delay hospital discharge. Chloroprocaine has a short duration of action and has re-emerged as an agent for ambulatory neuraxial anesthesia. There are limited data comparing intrathecal bupivacaine and chloroprocaine when used for cerclage placement. This retrospective study compares the time to hospital discharge between these drugs when used in spinal anesthesia for cervical cerclage placement. METHODS: A retrospective analysis of patients who underwent transvaginal cerclage placement under neuraxial anesthesia with intrathecal hyperbaric bupivacaine or plain chloroprocaine between January 1, 2015 and October 31, 2020. The primary outcome was the time to hospital discharge. Secondary outcomes included the incidence of inadequate anesthesia, postoperative pain scores and postoperative neurologic symptoms. RESULTS: Three hundred and sixty patients were included in the final analysis (bupivacaine n=236, chloroprocaine n=124). The median (IQR) intrathecal dose was 7.5 (7.5, 9) mg and 45 (45, 50) mg in the bupivacaine and chloroprocaine groups respectively. The time (median [IQR]) from spinal anesthesia to hospital discharge was significantly shorter in the chloroprocaine group compared with the bupivacaine group (218 [180, 253] vs. 370 [309, 424] min, P<0.001). There were no significant differences between the groups for secondary outcomes and neither group had a patient report neurologic symptoms. CONCLUSION: When utilized in spinal anesthesia for transvaginal cervical cerclage placement, chloroprocaine may reduce the time to discharge while providing comparable anesthesia to that provided by bupivacaine.

Respiratory depression after administration of single-dose neuraxial morphine for post-cesarean delivery analgesia: a retrospective cohort study.

BACKGROUND: Neuraxial administration of long-acting opioid is the "gold standard" for the management of postoperative pain following cesarean delivery. Respiratory depression, however, remains a concerning complication. METHODS: This retrospective single-center study of 4963 patients evaluated the frequency of respiratory depression after neuraxial morphine administration in a post-cesarean delivery population. The spinal dose of morphine varied from 100 to 450 µg intrathecally, and from 3 to 5 mg epidurally. The primary outcome was the initiation of a Rapid Response Team (RRT) event for respiratory failure due to neuraxial opioid in the 24 h following morphine administration. Secondary outcomes studied included oxygen desaturation events (SpO2 <90%), initiation of oxygen therapy and naloxone administration. RESULTS: There were no respiratory RRT events within the study period (95% confidence interval [CI] 0 to 7 per 10 000). There were no desaturation events recorded and no patients received supplemental oxygen therapy or naloxone (95% CI 0 to 7 per 10 000). CONCLUSION: Clinically significant respiratory depression is rare among patients receiving neuraxial morphine for post-cesarean delivery analgesia.

Remifentanil for fetal immobilization and analgesia during the ex utero intrapartum treatment procedure under combined spinal-epidural anaesthesia.

Remifentanil undergoes extensive placental transfer and has been used to provide fetal immobilization and anaesthesia for in utero fetal endoscopic interventions. We report three cases of the ex utero intrapartum treatment performed under neuraxial anaesthesia where the maternal administration of remifentanil was used to provide fetal immobilization and analgesia. Fetal pathology included goiter and arthrogryposis, with one case requiring a tracheostomy. The longest time on placental circulation was 21 min. No clinically significant maternal sedation or respiratory depression was observed. In all cases, remifentanil provided adequate fetal immobilization and obviated the need to administer other analgesics or neuromuscular blocking agents. Remifentanil is a useful adjunct for ex utero fetal procedures.

Intra-operative ketorolac 15 mg versus 30 mg for analgesia following cesarean delivery: a retrospective study.

BACKGROUND: Ketorolac is a nonsteroidal anti-inflammatory drug used as part of multimodal analgesia in women undergoing cesarean delivery. The lowest effective dose of ketorolac that best optimizes analgesia without increasing side effects is unclear. We performed this retrospective study to compare the analgesic efficacy of 15 mg or 30 mg ketorolac administered intra-operatively to our obstetric population. METHODS: We included patients who underwent cesarean delivery under neuraxial anesthesia and received 15 mg or 30 mg of ketorolac intra-operatively. Our multimodal analgesic regimen is standardized and includes 150 µg spinal or 3 mg epidural morphine, 975 mg rectal acetaminophen, and 15-30 mg intravenous ketorolac within 15 min of surgery completion. The primary outcome was opioid use in the first 6 h after surgery. Secondary outcomes were opioid use at 24 and 48 h, opioid dose, pain scores, breastfeeding, postoperative serum creatinine and need for rescue anti-emetics. RESULTS: One-thousand-three-hundred and forty-nine patients were analyzed (15 mg ketorolac n=999; 30 mg n=350). There was no difference between the two groups in patient demographics or intra-operative characteristics. There was no significant difference between groups for opioid use at 6 h after surgery (50.3% vs 52.0%, odds ratio [95% confidence interval] 1.13 [0.87 to 1.47]). There were also no significant differences between the groups for secondary outcomes. CONCLUSIONS: There was no difference in opioid use between patients receiving either a 15 mg or a 30 mg dose of ketorolac given intra-operatively for postoperative analgesia following cesarean delivery.