Optimal postoperative pain management after VATS lung resection by thoracic epidural analgesia, continuous paravertebral block or single-shot intercostal nerve block (OPtriAL): study protocol of a three-arm multicentre randomised controlled trial.

BACKGROUND: Adequate pain control after video-assisted thoracoscopic surgery (VATS) for lung resection is important to improve postoperative mobilisation, recovery, and to prevent pulmonary complications. So far, no consensus exists on optimal postoperative pain management after VATS anatomic lung resection. Thoracic epidural analgesia (TEA) is the reference standard for postoperative pain management following VATS. Although the analgesic effect of TEA is clear, it is associated with patient immobilisation, bladder dysfunction and hypotension which may result in delayed recovery and longer hospitalisation. These disadvantages of TEA initiated the development of unilateral regional techniques for pain management. The most frequently used techniques are continuous paravertebral block (PVB) and single-shot intercostal nerve block (ICNB). We hypothesize that using either PVB or ICNB is non-inferior to TEA regarding postoperative pain and superior regarding quality of recovery (QoR). Signifying faster postoperative mobilisation, reduced morbidity and shorter hospitalisation, these techniques may therefore reduce health care costs and improve patient satisfaction. METHODS: This multi-centre randomised study is a three-arm clinical trial comparing PVB, ICNB and TEA in a 1:1:1 ratio for pain (non-inferiority) and QoR (superiority) in 450 adult patients undergoing VATS anatomic lung resection. Patients will not be eligible for inclusion in case of contraindications for TEA, PVB or ICNB, chronic opioid use or if the lung surgeon estimates a high probability that the operation will be performed by thoracotomy. PRIMARY OUTCOMES: (1) the proportion of pain scores ≥ 4 as assessed by the numerical rating scale (NRS) measured during postoperative days (POD) 0-2; and (2) the QoR measured with the QoR-15 questionnaire on POD 1 and 2. Secondary outcome measures are cumulative use of opioids and analgesics, postoperative complications, hospitalisation, patient satisfaction and degree of mobility. DISCUSSION: The results of this trial will impact international guidelines with respect to perioperative care optimization after anatomic lung resection performed through VATS, and will determine the most cost-effective pain strategy and may reduce variability in postoperative pain management. Trial registration The trial is registered at the Netherlands Trial Register (NTR) on February 1st, 2021 (NL9243). The NTR is no longer available since June 24th, 2022 and therefore a revised protocol has been registered at ClinicalTrials.gov on August 5th, 2022 (NCT05491239). PROTOCOL VERSION: version 3 (date 06-05-2022), ethical approval through an amendment (see ethical proof in the Study protocol proof).

Transcatheter aortic valve implantation amid the COVID-19 pandemic: a nationwide analysis of the first COVID-19 wave in the Netherlands.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on healthcare systems. Most transcatheter aortic valve implantation (TAVI) centres have adopted different triage systems and procedural strategies to serve highest-risk patients first and to minimise the burden on hospital logistics and personnel. We therefore assessed the impact of the COVID-19 pandemic on patient selection, type of anaesthesia and outcomes after TAVI. METHODS: We used data from the Netherlands Heart Registration to examine all patients who underwent TAVI between March 2020 and July 2020 (COVID cohort), and between March 2019 and July 2019 (pre-COVID cohort). We compared patient characteristics, procedural characteristics and clinical outcomes. RESULTS: We examined 2131 patients who underwent TAVI (1020 patients in COVID cohort, 1111 patients in pre-COVID cohort). EuroSCORE II was comparable between cohorts (COVID 4.5 ± 4.0 vs pre-COVID 4.6 ± 4.2, p = 0.356). The number of TAVI procedures under general anaesthesia was lower in the COVID cohort (35.2% vs 46.5%, p < 0.001). Incidences of stroke (COVID 2.7% vs pre-COVID 1.7%, p = 0.134), major vascular complications (2.3% vs 3.4%, p = 0.170) and permanent pacemaker implantation (10.0% vs 9.4%, p = 0.634) did not differ between cohorts. Thirty-day and 150-day mortality were comparable (2.8% vs 2.2%, p = 0.359 and 5.2% vs 5.2%, p = 0.993, respectively). CONCLUSIONS: During the COVID-19 pandemic, patient characteristics and outcomes after TAVI were not different than before the pandemic. This highlights the fact that TAVI procedures can be safely performed during the COVID-19 pandemic, without an increased risk of complications or mortality.

Applying a physiological model to quantify the delay between changes in end-expired concentrations of sevoflurane and bispectral index.

BACKGROUND: The delay between changes in end-expired sevoflurane concentrations and bispectral index (BIS) may be characterized by a 'rate constant' (ke0). A smaller ke0 reflects a longer delay. Values for ke0 vary substantially among studies. The question arises how ke0 depends on experimental conditions, including ventilation and apparatus. METHODS: Increasing and decreasing sevoflurane concentrations were cyclically delivered to our validated model. First, we quantified theoretical ke0 values for distinct alveolar ventilations, estimating ke0 from sevoflurane tensions in alveolar space and grey matter. Secondly, we investigated the impact of experimental conditions. To predict BIS, the model was extended with a pharmacodynamic section, including ke0. Known values, matching theoretical values, were assigned to this ke0. These were recovered from end-expired concentrations and BIS. Possible determinants of error (difference between assigned and recovered ke0) were varied, that is fraction of dead space gas in end-expired gas (d), and time delays in measuring BIS (tBIS) and end-expired concentrations (tEE). RESULTS: Theoretical ke0s were 0.7, 0.53, 0.35, and 0.2 min(-1) for an arterial Pco2 of 8, 6.67, 5.33 (normocapnia), and 4 kPa, respectively. For spontaneous ventilation, ke0 = 0.53 min(-1). Recovered ke0s depended on d and Deltat (= tBIS - tEE) and were smaller than assigned values (if Deltat > 0). Errors increased with increasing d and Deltat. For normocapnia, ke0 was between 0.32 and 0.23 min(-1) (d = 0.1; any Deltat = 0-60 s). For spontaneous ventilation, ke0 was between 0.51 and 0.40 min(-1) (d = 0-0.1; Deltat = 5-20 s). CONCLUSIONS: Published ke0s (0.22-0.53 min(-1)), including our own for sevoflurane-depressed spontaneous ventilation (0.48 min(-1)), are in the ranges dictated by investigation-specific conditions.

Multi-level approach to anaesthetic effects produced by sevoflurane or propofol in humans: 1. BIS and blink reflex.

BACKGROUND: The relative roles of forebrain and brainstem in producing adequate anaesthesia are unclear. METHODS: We simultaneously analysed the effects of sevoflurane (Group S; n = 18) or propofol (Group P; n = 29) on the bispectral index (BIS) and the first component of the blink reflex (R1). The dose of anaesthetic agent was increased until loss of blink reflex. After discontinuation and reappearance of blink reflex activity, the amount was increased again. The area under curve R1 (area-R1) of the electromyogram of the orbicularis oculi muscle after electrical stimulation of the supraorbital nerve was measured. Using a sigmoid E(max) model and a first-order rate constant k(e0), we characterized the dose-response relationships for BIS and area-R1. RESULTS: Concentration-dependent depression of BIS and area-R1 was adequately modelled. The concentration that causes an effect midway between minimum and maximum (EC50) for area-R1 was smaller than EC50 for BIS in both groups [0.34 (0.19) vs 1.29 (0.19) vol% and 1.78 (0.65) vs 2.69 (0.67) mug ml(-1); mean (sd)]. At doses of sevoflurane and propofol with equivalent depression of BIS, sevoflurane depressed area-R1 more than propofol. The k(e0) for area-R1 was about half that for BIS in both groups: 0.24 (0.19-0.29) vs 0.48 (0.38-0.60) min(-1) for Group S; 0.28 (0.23-0.34) vs 0.46 (0.40-0.54) min(-1) for Group P, geometric mean (95% CI). CONCLUSIONS: The blink reflex (brainstem function) is more sensitive to sevoflurane or propofol than BIS (forebrain function). Sevoflurane suppresses the blink reflex more than propofol. Different k(e0)s for blink reflex vs BIS indicate different effect sites.

Multi-level approach to anaesthetic effects produced by sevoflurane or propofol in humans: 2. BIS and tetanic stimulus-induced withdrawal reflex.

BACKGROUND: General anaesthesia could be assessed at two sites: cortical structures and the spinal cord. However, the practicalities of measurement at these two sites differ substantially. METHODS: We simultaneously analysed effects of sevoflurane (Group S; n = 16) or propofol (Group P; n = 17) on bispectral index (BIS) and the tetanic stimulus-induced withdrawal reflex (TIWR). TIWR was quantified by the area under the curve of the electromyogram of the biceps femoris muscle after electrical stimulation of the sural nerve. After loss of consciousness, TIWR was evoked once per minute. The anaesthetic was increased until TIWR disappeared. After discontinuation of the anaesthetic and reappearance of TIWR, the amount of anaesthetic was increased again. Using a sigmoid E(max) model and a first-order rate constant k(e0), we characterized the dose-response relationships for BIS and TIWR. RESULTS: Concentration-dependent depression of TIWR was reasonably well modelled for sevoflurane, but poorly for propofol. TIWR was completely suppressed by sevoflurane, but not propofol. Sevoflurane reduced TIWR to 5 mV ms (very weak movement) at 1.68 vol% end-expired concentration [approximately minimum alveolar concentration (MAC value)]. The k(e0)s for TIWR were smaller than those for BIS: 0.25 (0.16-0.39) vs 0.41 (0.33-0.51) min(-1) for Group S; 0.25 (0.22-0.30) vs 0.34 (0.29-0.40) min(-1) for Group P [geometric mean (95% CI)]. CONCLUSIONS: High concentrations of sevoflurane depress TIWR more than propofol. With propofol, we frequently observed a paradoxical behaviour of muscles of the lower leg. TIWR lags behind BIS, indicating different effect sites for two intended anaesthetic effects: unresponsiveness to noxious stimulation and unconsciousness.

Electromyographic assessment of blink reflexes correlates with a clinical scale of depth of sedation/anaesthesia and BIS during propofol administration.

BACKGROUND: General anaesthesia is characterized by loss of consciousness, amnesia and obtundation of reflex responses to noxious stimuli. Quantifying the blink reflex may reflect the depression of reflex arches induced by anaesthetics and thus being informative on the anaesthetic state. METHODS: The relation between the electrically evoked blink reflexes and the depth of sedation and anaesthesia induced with intravenous propofol was investigated. Twenty patients received propofol by target-controlled infusion to create a stepwise deepening of sedation and anaesthesia. Depth of anaesthesia was assessed using the observer's assessment of anaesthesia and sedation (OAAS) scale, and by bispectral EEG analysis (BIS). Probit analysis was used to estimate the predicted propofol effect site concentrations producing unconsciousness, no response to noxious stimulation, and loss of blink reflex components. RESULTS: Latency of the first (R1) and second (R2) blink component increased, whereas duration and area decreased with increasing depth of sedation and anaesthesia. A reasonably strong correlation between OAAS and the areas of R1 and R2 components was found (Spearman's rho = 0.92 and 0.89). The areas of R1 and R2 and the OAAS also correlated with BIS (Spearman's rho = 0.91, 0.88 and 0.90). EC(50) and EC(95) for loss of R1 were 2.8 (95% CI: 2.5-3.2) micro g/ml and 4.6 (95% CI: 4.1-5.5) micro g/ml, respectively. CONCLUSIONS: Our results suggest that the differential sensitivity of the components of the blink reflex could be useful in monitoring depth of sedation and light levels of anaesthesia during the administration of propofol. Both OAAS and BIS correlate similarly with the blink reflex components.

Electromyographic assessment of blink and corneal reflexes during midazolam administration: useful methods for assessing depth of anesthesia?

BACKGROUND: There are at least three components of the anesthetic state: loss of consciousness, amnesia and obtundation of reflex responses to noxious stimuli. To investigate the third component, we used a standard electrical stimulus to evoke a blink reflex, which was electromyographically recorded. These data may give information on the anesthetic state. METHODS: The relation between the electrically evoked blink and corneal reflexes and the depth of sedation and anesthesia induced with intravenous midazolam was investigated. Ten patients received i.v. increments of midazolam (1 mg, 2 mg, 3 mg, 3 mg, 3 mg, etc., until a 21-mg total dose) to create a step-wise deepening of sedation and anesthesia. Depth of anesthesia was assessed by the Observer's Assessment of Alertness/Sedation (OAAS) scale, ranging from 5 ( = awake and alert) to 0 ( = no motor response to tetanic stimulation). RESULTS: Latency of the first (R1) and second (R2) blink components and the corneal (C) reflex component increased, whereas duration and area decreased with increasing depth of sedation and anesthesia. R1 was last seen at an OAAS score [mean (SD)] of 1.8 (0.8), R2 at a score of 3.1 (1.1), C at a score of 3.8 (0.8), and R3 at 4.8 (0.5). These end-points were all statistically different from each other, except R2 vs. C. CONCLUSIONS: Our results suggest that the differential sensitivity of the components of the blink reflex could be useful to monitor depth of sedation and light levels of anesthesia during the administration of midazolam.

Epidural bupivacaine, sufentanil or the combination for post-thoracotomy pain.

Analgesia with epidural bupivacaine, sufentanil or the combination was studied in 50 patients who had undergone thoracotomy. During operation all patients received an initial dose of bupivacaine 0.5% with adrenaline 5 micrograms.ml-1 (5-10 ml) by thoracic epidural catheter. One hour later the patients were divided into three groups: the bupivacaine group (bupivacaine 0.125%), the sufentanil group (50 micrograms sufentanil in 60 ml normal saline) and the combination group (50 micrograms sufentanil in 60 ml bupivacaine 0.125%). Analgesia in the three groups was provided by a continuous epidural infusion (5-10 ml.h-1) for 3 days. The mean dose of bupivacaine was significantly higher (P less than 0.05) in the bupivacaine group (12.07 mg.h-1 (s.e.mean 0.97 mg.h-1)), compared with the combination group (9.82 mg.h-1 (s.e.mean 0.43 mg.h-1)). The mean dose of sufentanil in the sufentanil group was similar to the combination group (6.37 micrograms.h-1 (s.e.mean 0.23 micrograms.h-1) and 6.52 micrograms.h-1 (s.e.mean 0.28 micrograms.h-1), respectively. The pain scores on the inverse visual analogue scale of most patients in the bupivacaine group were unacceptably low. The sufentanil group had much better pain scores, but on exercise these patients experienced more pain than the combination group. The combination group had, overall, better pain scores. In the combination group, there were better respiratory results.

Migration of thoracic epidural catheters. Three methods for evaluation of catheter position in the thoracic epidural space.

Migration of thoracic epidural catheters was evaluated in 25 patients by three methods either after placement of the catheter or immediately after surgery. The first method was the determination of the depth of the catheter from the skin, the second the determination of the level of sensory blockade which resulted from a test dose of a local anesthetic agent, while the third consisted of radiological visualisation of the catheter tip in the epidural space with radiopaque dye. The evaluations were repeated on the third or fourth day after operation. We observed an inward movement of the catheter in 56% of the patients instead of the expected outward movement. This inward movement was accompanied by a higher level of sensory blockade. No relationship with radiological visualisation was found.