Implications of nocebo in anaesthesia care.

Nocebo refers to non-pharmacological adverse effects of an intervention. Well-intended procedural warnings frequently function as a nocebo. Both nocebo and placebo are integral to the generation of 'real' treatment effects and their associated 'real' side-effects. They are induced or exacerbated by: context; negative expectancy; and negative conditioning surrounding treatment. Since the late 1990s, the neuroscience literature has repeatedly demonstrated that the nocebo effect is mediated by discrete neurobiological mechanisms and specific physiological modulations. Although no single biological mechanism has been found to explain the nocebo effect, nocebo hyperalgesia is thought to initiate from the dorsal lateral prefrontal cortex subsequently triggering the brain's descending pain modulatory system and other pain regulation pathways. Functional magnetic resonance imaging shows that expectation of increased pain is accompanied by increased neural activity in the hippocampus and midcingulate cortex which is not observed when analgesia is expected. Functional magnetic resonance imaging studies have shown that the anterior cingulate cortex is pivotal in the perception of affective pain evoked by nocebo words. Research has also explored neurotransmitters which mediate the nocebo effect. The neuropeptide cholecystokinin appears to play a key role in the modulation of pain by nocebo. Hyperalgesia generated by nocebo also increases the activity of the hypothalamic-pituitary-adrenal axis as indicated by increases in plasma cortisol. The avoidance or mitigation of nocebo needs to be recognised as a core clinical skill in optimising anaesthesia care. Embracing the evidence around nocebo will allow for phrases such as 'bee sting' and 'sharp scratch' to be thought of as clumsy verbal relics of the past. Anaesthesia as a profession has always prided itself on practicing evidence-based medicine, yet for decades anaesthetists and other healthcare staff have communicated in ways counter to the evidence. The premise of every interaction should be 'primum non nocere' (first, do no harm). Whether the context is research or clinical anaesthesia practice, the nocebo can be ignored no longer.

Nocebo language in anaesthetic patient written information.

Recent evidence suggests that how anaesthesia information is presented may influence patient treatment outcomes. We conducted an observational study of anaesthetic-based patient information leaflets across NHS Trusts in England for their nocebo terms vs. therapeutic terms, and how adverse effects were presented. In this study, 'nocebo' is wording that may predispose the patient to expect adverse events such as pain or nausea. Data were extracted and analysed for word frequency, weighted proportion and thematic analysis. In total, 42 patient information leaflets from 61 NHS Trusts were analysed. 'Pain' was the second most common word across the leaflets, median (IQR [range]) 0.82 (0.50-1.0 [0.12-1.47]) per 100 words, second only to 'anaesthesia'. In comparison, 'safe' was the most common positively valanced word which featured eight times less frequently than 'pain' 0.10 (0.07-0.18 [0.0-0.84]) and 'comfort' featured 16.5 times less than 'pain' 0.02 (0.0-0.05 [0.0-0.13]). Multiple examples of phrasing that could have potential nocebo effects included, 'you will need strong painkillers' suggesting 'strong pain' and the need for 'painkillers' rather than using therapeutic terms focusing on 'comfort', 'healing' and 'recovery'. Our results suggest a dominance of phrases with negative content in the presentation of anaesthesia information provided to patients. Clinicians need to be aware of inadvertent generation of nocebo-weighted vs. comfort-weighted communication with patients. Our study findings suggest an opportunity for more emphasis to be placed on therapeutic outcomes and effective mitigation strategies of anaesthesia risks to avoid potential unintended nocebo effects of anaesthesia information leaflets or websites.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort.

BACKGROUND: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality. CONCLUSIONS: As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery.

A comparison of fentanyl with pethidine for pain relief during childbirth: a randomised controlled trial.

OBJECTIVE: To compare the efficacy of fentanyl administered via the subcutaneous (s.c.) or intranasal (i.n.) route with intramuscular (i.m.) pethidine in labouring women requesting analgesia. DESIGN: A randomised controlled trial three-armed, parallel-design. SETTING: A regional hospital and the largest tertiary maternity centre in South Australia. SAMPLE: One hundred and fifty-six healthy parturients birthing at term. METHODS: Women were randomised to receive s.c. fentanyl (n = 53), i.n. fentanyl (n = 52), or i.m. pethidine (n = 51). The outcomes were analysed by intention-to-treat. MAIN OUTCOME MEASURES: Pain scores measured before and 30 minutes after opioid administration. RESULTS: All groups reported clinically significant reductions in pain scores (mean range 1.2-1.6; P < 0.001), with no significant differences between groups. Significantly more women in the fentanyl groups reported satisfaction with using the study drug again, compared with women receiving i.m. pethidine (82.9% i.n. fentanyl, 80.6% s.c. fentanyl, and 44.0% i.m. pethidine; P < 0.01). Women in the fentanyl groups experienced less sedation (i.n. fentanyl 7.3%, s.c. fentanyl 2.9%, i.m. pethidine 44%; P ≤ 0.03), shorter labours by at least 2 hours (P < 0.05), and fewer difficulties establishing breastfeeding (78.8% i.m. pethidine, 39.4% i.n. fentanyl, and 44.0% s.c. fentanyl; P < 0.01). Neonates in the pethidine group were more likely to require nursery admission (P < 0.02). CONCLUSIONS: Fentanyl administered by s.c. and i.n. routes is as efficacious in relieving labour pain as i.m. pethidine, but resulted in greater satisfaction, less sedation, shorter labour, fewer nursery admissions, and fewer difficulties in establishing breastfeeding. Fentanyl appears to be a suitable alternative to pethidine when providing parenteral pain relief to labouring women.

Hypnosis antenatal training for childbirth: a randomised controlled trial.

OBJECTIVE: To determine the use of pharmacologic analgesia during childbirth when antenatal hypnosis is added to standard care. DESIGN: Randomised controlled clinical trial, conducted from December 2005 to December 2010. SETTING: The largest tertiary referral centre for maternity care in South Australia. POPULATION: A cohort of 448 women at >34 weeks of gestation, with a singleton pregnancy and cephalic presentation, planning a vaginal birth. Exclusions were: the need for an interpreter; pre-existing pain; psychiatric illness; younger than 18 years; and previous experience of hypnosis for childbirth. METHODS: All participants received usual care. The group of women termed Hypnosis + CD (hypnotherapist guided) were offered three antenatal live hypnosis sessions plus each session's corresponding audio CD for further practise, as well as a final fourth CD to listen to during labour. The group of women termed CD only (nurse administered) were played the same antenatal hypnosis CDs as group 1, but did not receive live hypnosis training. The control group participants were given no additional intervention or CDs. MAIN OUTCOME MEASURE: Use of pharmacological analgesia during labour and childbirth. RESULTS: No difference in the use of pharmacological analgesia during labour and childbirth was found comparing hypnosis + CD with control (81.2 versus 76.2%; relative risk, RR 1.07; 95% confidence interval, 95% CI 0.95-1.20), or comparing CD only with control (76.9 versus 76.2%, RR 1.01, 95% CI 0.89-1.15). CONCLUSIONS: Antenatal group hypnosis using the Hypnosis Antenatal Training for Childbirth (HATCh) intervention in late pregnancy does not reduce the use of pharmacological analgesia during labour and childbirth.

Pain vs comfort scores after Caesarean section: a randomized trial.

BACKGROUND: The use of negative words, such as 'sting' and 'pain', can increase patient pain and anxiety. We aimed to determine how pain scores compare with comfort scores and how the technique of pain assessment affects patient perceptions and experiences after operation. METHODS: After Caesarean section, 300 women were randomized before post-anaesthesia review. Group P women were asked to rate their pain on a 0-10-point verbal numerical rating scale (VNRS), where '0' was 'no pain' and '10' was 'worst pain imaginable'. Group C women were asked to rate comfort on a 0-10-point VNRS, where '0' was 'no comfort' and '10' was 'most comfortable'. All women were asked whether the Caesarean wound was bothersome, unpleasant, associated with tissue damage, and whether additional analgesia was desired. RESULTS: The median (inter-quartile range) VNRS pain scores was higher than inverted comfort scores at rest, 2 (1, 4) vs 2 (0.5, 3), P=0.001, and movement, 6 (4, 7) vs 4 (3, 5), P<0.001. Group P women were more likely to be bothered by their Caesarean section, had greater VNRS 'Bother' scores, 4 (2, 6) vs 1 (0, 3), P<0.001, perceived postoperative sensations as 'unpleasant' [relative risk (RR) 3.05, 95% confidence interval (CI) 2.20, 4.23], P<0.001, and related to tissue damage rather than healing and recovery (RR 2.03, 95% CI 1.30, 3.18), P=0.001. Group P women were also more likely to request additional analgesia (RR 4.33, 95% CI 1.84, 10.22), P<0.001. CONCLUSIONS: Asking about pain and pain scores after Caesarean section adversely affects patient reports of their postoperative experiences.

Assessment of block height for satisfactory spinal anaesthesia for caesarean section.

We investigated block heights that anaesthetists considered adequate for caesarean section to proceed under spinal anaesthesia. During 3 months, 15 obstetric anaesthetists recorded block height to touch, pinprick or cold when spinal anaesthesia was considered satisfactory for caesarean section to proceed. Median (IQR [range]) block height for touch, pinprick, first cold and icy were: T10 (T7-T12 [T3-L1]); T5 (T4-T6 [C7-L1]); T5 (T4-T6 [C7-L1]); and T3 (T2-T4 [C7-L1]), respectively. Modalities were significantly correlated for: touch and cold, p = 0.0001; touch and icy, p = 0.0007; touch and pinprick, p = 0.0018; cold and icy, p < 0.0001; cold and pinprick, p = 0.0001; icy and pinprick, p < 0.0001. Pairwise comparisons showed differences between all modalities (p < 0.001) apart from pinprick and first cold (p = 0.94). All women had satisfactory anaesthesia despite 76 (81%) having a block to touch below T6. Single modality assessment of block height, particularly using touch, may erroneously indicate inadequate anaesthesia for caesarean section.

Anaesthetists' risk assessment of placebo nerve block studies using the SHAM (Serious Harm and Morbidity) scale.

The SHAM (Serious Harm and Morbidity) scale was developed to categorise the severity of potential complications of placebo control interventions in the context of local anaesthesia research. A convenience sample of 43 anaesthetists used the SHAM scale to grade ten published randomised controlled trials investigating local anaesthesia nerve blocks. The Fleiss κ statistic assessed agreement between these anaesthetists and probability of random agreement (Pr(e)) when using the SHAM scale; a κ > 0 shows concordance between assessors above random agreement. Overall κ was 0.50 (95% CI 0.49-0.51, p < 0.001), Pr(e) = 0.21. There was moderate agreement between assessors in determining whether studies were low-risk (SHAM score 0-2) or high-risk (SHAM score 3-4) (κ 0.60 (95% CI 0.58-0.62), Pr(e) = 0.51). Compared with anaesthetists given clinical examples of interventions when applying the SHAM score, anaesthetists who were not given examples showed significantly less inter-individual agreement (κ 0.76 (95% CI 0.72-0.81), Pr(e) = 0.5 vs 0.45 (95% CI 0.41-0.49), Pr(e) = 0.52, p < 0.0001). These results suggest that the SHAM score can be successfully used to grade the severity of potential complications of placebo-controlled interventions in local anaesthesia research and represent a first step towards the score's validation.

Communications during epidural catheter placement for labour analgesia.

Evidence suggests that anaesthetists' communication can affect patient experience. There is a lack of guidance for anaesthetists as to the optimal verbal communication to use during insertion of epidurals on the labour ward. We recorded the verbal communication used by 14 anaesthetists during the siting of epidural catheters in women on the labour ward; a classification of the language used was subsequently devised. We found that commands and information statements were the most common types of communication used. Individual anaesthetists differed markedly in their use of positive and negative verbal language. This classification of verbal communication that we produced may be of value in future training and research of verbal communication used by anaesthetists on the labour ward.

Use of invasive placebos in research on local anaesthetic interventions.

Placebos play a vital role in clinical research, but their invasive use in the context of local anaesthetic blocks is controversial. We assessed whether recently published randomised controlled trials of local anaesthetic blocks risked harming control group patients in contravention of the Declaration of Helsinki. We developed the 'SHAM' (Serious Harm and Morbidity) scale to assess risk: grade 0 = no risk (no intervention); grade 1 = minimal risk (for example, skin allergy to dressing); grade 2 = minor risk (for example, subcutaneous haematoma, infection); grade 3 = moderate risk (with or without placebo injection) (for example, neuropraxia); and grade 4 = major risk (such as blindness, pneumothorax, or liver laceration). Placebo interventions of the 59 included trials were given a SHAM grade. Nine hundred and nineteen patients in 31 studies, including six studies with 183 children, received an invasive placebo assessed as SHAM grade ≥ 3. A high level of agreement (78%, κ = 0.80, p < 0.001) for SHAM grades 0-4 increased to 100% following discussion between assessors. More than half of the randomised controlled study designs subjected patients in control groups to risks of serious or irreversible harm. A debate on whether it is justifiable to expose control group patients to risks of serious harm is overdue.

Subcutaneous fentanyl for labour analgesia: a retrospective case note review.

BACKGROUND: In 2017, a South Australia Perinatal Practice Guideline was introduced state-wide for the use of subcutaneous fentanyl for labour analgesia as a replacement for intramuscular pethidine. We retrospectively reviewed the implementation of this practice change in our institution. METHODS: A retrospective review of maternal and neonatal case notes for the first 100 women administered subcutaneous fentanyl in labour at a single tertiary referral centre for maternity care, between February and June 2017. RESULTS: Of the 102 women administered subcutaneous fentanyl, the majority (55%) were primipara, with an average maternal age of 29 years and body mass index of 27 kg/m2. The median total fentanyl dose administered was 200 µg and the average time from last dose to birth was 3 h. The majority of women (70%) did not require additional rescue labour analgesia and 80% had a spontaneous vaginal birth. All neonates had a 5-min Apgar score >7. The median Apgar score at 1 and 5 min was 9. No neonate had an arterial cord blood pH <7.1. The mean arterial and venous cord blood pH was 7.3. The average time for neonates to establish breathing was 1 min and the median postnatal length of stay was two days. CONCLUSIONS: Subcutaneous fentanyl for labour analgesia appears effective and has a low incidence of adverse events.

Fentanyl concentration in maternal and umbilical cord plasma following intranasal or subcutaneous administration in labour.

BACKGROUND: The effect that the route of maternal fentanyl administration has on placental transfer of drug to the neonate is not well studied. Plasma concentration ratios are an indicator of fetal exposure, relative to the mother. METHODS: A cohort study (n=30) was conducted to measure fentanyl concentrations in maternal plasma, and arterial and venous cord blood, among women administered either intranasal or subcutaneous fentanyl for labour pain relief. Maternal and cord blood samples were collected within 30 min of birth to determine the fentanyl plasma concentration and to assess relative neonatal exposure. Neonatal outcomes were assessed by Apgar scores, need for resuscitation and nursery admission. RESULTS: Thirty paired samples were obtained from healthy parturients with uncomplicated term pregnancies. Highest observed umbilical venous and arterial concentrations were 0.71 ng/mL and 0.56 ng/mL, respectively, and fetal to maternal fentanyl plasma concentration ratios ranged between 0.23 and 0.73, indicating low fetal exposure. While the total intranasal fentanyl dose administered was significantly higher than the subcutaneous fentanyl dose, this did not result in a higher fetal to maternal ratio. All neonates in both groups had 5-min Apgar scores >7, two neonates required short-term stimulation and oxygen (unrelated to fentanyl) and no neonate was admitted to the nursery. CONCLUSION: This study is the first to examine fetal and maternal fentanyl concentrations after subcutaneous administration. This research supports the safe use of fentanyl for labour analgesia for women.

Open vs specific questioning during anaesthetic follow-up after Caesarean section.

Words with negative emotional content such as pain or itch may enhance perception of these symptoms. We assessed open and direct questioning for symptoms in 100 women following Caesarean section. Of the 65 women reporting pain, 25 (39%) did so only when questioned specifically. Similarly, three women with bothersome pain (5%), and two requesting analgesia (3%), failed to disclose pain until questioned specifically. None of the 46 women with pain scores < 6 on a verbal numerical rating scale requested additional analgesia. Of 31 women with pruritus, two (6%) stated it bothered them and requested treatment and one (3%) failed to disclose pruritus on open questioning. Most women with bothersome pain or who request analgesia reveal this with open questioning. However, specific questioning is required to elicit pain in all patients. Most patients are bothered by pain at pain scores >or= 6, while those with scores < 6 are unlikely to request additional analgesia.

Communication skills for the anaesthetist.

Anaesthetists have traditionally focused on technological and pharmacological advances when considering the provision of anaesthetic care. Anaesthetists are expected to be able to communicate effectively with peers, patients, their families and others in the medical community; however, few details are provided regarding how this might be achieved. Recent evidence suggests that communication practices should include a consideration of conscious and subconscious processes and responses. This model has potential relevance when learning and teaching how to communicate effectively in the stressful environment of anaesthetic clinical practice, and includes: reflective listening; observing; acceptance; utilisation; and suggestion. Understanding these processes could allow the development of a learnable framework for effective communication when the usual strategies are not working. This concept could also be used to facilitate communicating with surgeons and other colleagues, with potential benefits to patients.