This study followed the STROBE statements [7].
Patient selection
This study is a monocentric prospective observational cohort study conducted at Tenon Hospital, Paris, France. Consecutive patients over 18 years old and suffering from pneumothorax requiring VATS treatment between February 2017 and April 2018 were included in the study. The exclusion criteria were: secondary pneumothorax, pregnancy, chronic preoperative analgesic treatment and opioid addiction, associated hemothorax, supra-segmental parenchymal resection and the lack of social health insurance coverage. Intraoperative conversions of VATS into thoracotomy and revision surgery within the first postoperative 72 h were also excluded from the study.
Anesthesia, surgery and analgesia management
Except for the choice of the postoperative loco-regional analgesic technique, the anesthetic management of patients undergoing VATS for pneumothorax is standardized in our institution. All the patients were anesthetized using a targeted concentration infusion of propofol (Fresenius Kabi; Bad Homburg vor der Höhe, Germany) and sufentanil (Mylan; Canonsburg, PA, USA), while the depth of anesthesia was monitored with a bispectral index coupled with standard anesthetic monitoring. Atracurium (Hospira; Lake Forest, IL, USA) was used for muscle relaxation. Dexamethasone 8 mg IV (Mylan) was systematically used to reduce postoperative nausea and vomiting. Intraoperative ketamine administration (0.3 mg/kg – Panpharma; Boulogne-Billancourt, France) was considered as a co-analgesic except in cases of high blood pressure in the operating room, or significant active cannabis intoxication. Oral postoperative multimodal analgesia routinely included acetaminophen (1 g 4 times a day – Sanofi-Aventis, Paris, France), nefopam (20 mg 4 times a day – Biocodex; Gentilly, France) and tramadol (50 mg 4 times a day – Meda Pharma, Solna, Sweden). Intraoperative IV lidocaine (0.3 to 0.5 mg/kg – Aguettant; Lyon, France) and postoperative ketoprofen (50 mg 4 times a day – Sanofi-Aventis) administrations were left to the discretion of the attending anesthesiologist. All patients were immediately extubated at the end of the surgical procedure.
Surgery was conducted under one-lung ventilation after intubation with a double-lumen tube. Single-port VATS was the first choice method; multi-port surgery being reserved for cases when that failed. VATS was standardized as previously described [8], with a 1.5–2 cm single incision performed on the axillary anterior line in the seventh intercostal space. Wound retractors were used to protect intercostal tissues. All the instruments were introduced through this single port. Surgery consisted of resection of apical parenchymal dystrophies using an articulated stapler, followed by a talc effusion pleurodesis. A single 24F chest tube was introduced through the single incision under visual control at the end of the procedure.
The loco-regional analgesic technique was left to the discretion of the physician in charge of the patient and was performed at the end of the surgical procedure. A paravertebral block was performed by the surgeon through a transparietal approach with insertion of a catheter under direct vision until placement of the tip into the paravertebral space [9], and then injected with an initial bolus of 15 mL lidocaine 20 mg/mL + epinephrine 50 μg/mL (Aguettant), followed by a continuous injection of 10 mL/h ropivacaine 2 mg/mL (Fresenius Kabi) through an elastomeric pump. A serratus plane block was performed by the injection of local anesthetics between the serratus anterior and the latissimus dorsi muscles, with ultrasound guidance, as described initially by Blanco et al. [10]. A serratus plane block was performed either by single injection (ropivacaine 2 mg/mL, 20 mL for patients under 175 cm and 30 mL for patients taller than 175 cm) or by injection of an initial bolus (lidocaine 20 mg/mL + epinephrine 50 μg/mL, 15 mL) followed by the placement of a catheter between the two muscles and the continuous injection of 10 mL/h ropivacaine 2 mg/mL through an elastomeric pump. In addition, 10 mg on-demand oral rapid-release morphine (Actiskenan®, Ethypharm, Saint-Cloud, France) was given to patients in case of residual pain (Visual Analog Scale (VAS) value > 3/10). We predefined a threshold of 50 mg of morphine over the first 3 postoperative days as being “high-dose morphine consumption”, based on the mean amount of morphine consumption observed in our institution and the limited data available from recent studies reporting postoperative morphine consumptions in patients scheduled for VATS [11, 12].
Data collection
We collected demographic data (age, sex, weight, height, body mass index), as well as information about active smoking status and chronic drugs consumption (especially cannabinoids and opioids) for each patient. The following surgical data were also collected: the number, side and site of surgical incisions and thoracic drains, the duration of surgery, the surgical technique used (pleurodesis or pleural abrasion, with or without resection of dystrophic parenchyma) and the duration of postoperative drainage. We also recorded the anesthetic and analgesic agents administered to patients during anesthesia, such as ketamine, intravenous lidocaine, dexamethasone, paracetamol, nefopam, tramadol, ketoprofen and/or morphine.
The morphine titration cumulative dose and pain intensity score (graded from 0 to 10 on a VAS) at rest and on coughing were collected in the recovery room upon the patient’s arrival and after one hour. Finally, pain VAS values were also collected at rest and on coughing in the wards at 2, 12, 24, 48 and 72 h after surgery. Cumulative oral morphine consumption was collected as well as daily and total doses of other analgesics such as acetaminophen, nefopam, tramadol, IV lidocaine and ketoprofen. The occurrence of nausea, vomiting and urinary retention were noted for each patient. The hospital length-of-stay was recorded.
Definition of endpoints and statistical analysis
The primary endpoint was the cumulative oral morphine consumption (expressed in mg) during the first postoperative 72 h. The secondary endpoints were: 1) the intensity of postoperative pain at rest and on coughing, and 2) the incidence of side effects most frequently associated with opioid consumption such as nausea, vomiting and urinary retention. Quantitative data were expressed as median values [25-75th percentiles] and qualitative data were expressed as numbers (percentages). Primary and secondary endpoints for each analgesic technique used were compared using the Kruskall-Wallis test with Dunn’s correction. We defined a priori a morphine consumption > 50 mg within the first postoperative 72 h as a reasonable marker of difficult pain control and high-dose morphine consumption. Factors associated with a high-dose morphine consumption were assessed by univariate logistic regression and chi-square for quantitative and qualitative variables, respectively. All variables with p value ≤0.2 were integrated into the multivariate step by step forward logistic regression model. P < 0.05 was considered significant. Statistical analysis was performed using SPSS version 23 (SPSS, IBM Corp, Armonk, NY).