RETRACTED ARTICLE: The effects of a recruitment manoeuvre with positive end-expiratory pressure on lung compliance in patients undergoing robot-assisted laparoscopic radical prostatectomy

Using lung protective ventilation (LPV) strategies in patients at risk of postoperative pulmonary complications undergoing major abdominal procedures has become an area of interest in recent years. However, controversy persists around which features of LPV are beneficial in this group, as the largest study utilised low tidal volumes [1], a recruitment manoeuvre (RM), and positive end-expiratory pressure (PEEP). Although there has been much recent research in this area, key uncertainties in perioperative ventilation remain.

Since the introduction of computer-enhanced robotic surgi-cal systems in 2001, robot-assisted laparoscopic radical prostatectomy (RARP) has been commonly used in the surgical treatment of prostate cancer. RARP presents several advantages over conventional surgery, including nerve sparing, shorter hospitalization times, reduced blood loss, and less postoperative pain [2, 3]. However, to maximize the surgical visual field, RARP usually requires the patient to be placed in a steep Trendelenburg lithotomy position with a pneumoperitoneum.

Both the increase in abdominal pressure because of a pneumoperitoneum with CO₂ insufflation and the steep Trendelenburg lithotomy position during RARP have been shown to impair respiratory function, mainly inducing atelectasis formation in the dependent lung regions [4].

Recent clinical data have demonstrated that a mechanical ventilatory strategy using lower tidal volumes and PEEP decreases the risk of pulmonary complications by minimising alveolar stretching at the end of inspiration and thus avoiding possible inflammation or alveolar collapse [5]. Using PEEP after recruitment can reportedly prevent re-collapse of the alveoli [6‐8]. The distinct differences seen in compliance at identical pressure levels before and after recruitment support the idea of a gain in the number of open alveoli by the RM itself [9]. Recent clinical studies have also reported that mechanical ventilation using PEEP with or without an RM could help improve intraoperative arterial partial pressure of oxygen (PaO₂) and lung compliance (C_LUNG) and reduce pulmonary shunt fraction [10, 11]. However, the effects of an RM with PEEP on C_LUNG are not well characterised in patients undergoing RARP. To the best of our knowledge, the effects of an RM with PEEP on C_LUNG in patients undergoing RARP have not been thoroughly investigated.

Therefore, the aim of this study was to evaluate the effects of an RM on respiratory and ventilatory parameters and arterial blood gas analysis in patients undergoing RARP.

This single-centre, prospective, randomized, comparative clinical and observational study was approved by the Ethics Committee of Juntendo University Hospital. Written informed consent was obtained from all 19 adult male patients enrolled in the study. This registered clinical trial (UMIN000013888) included consecutive patients undergoing RARP from November 2013 to May 2014. We enrolled non-smoking patients aged 20–70 years with an American Society of Anesthesiologists (ASA) Physical Status Classification score of 1–2 who were scheduled for RARP using a computer-enhanced robotic operating system (da Vinci™ Surgical System, Intuitive Surgical, Inc., Sunnyvale, CA, USA). Patients with a known history of chronic obstructive pulmonary disease, renal or heart failure, or obesity [defined as a body mass index (BMI) ≥ 30 kg m⁻²] were excluded from the study. No premedication was given. Upon arriving in the operating theatre, patients were monitored by electrocardiography, pulse oximetry, capnography, non-invasive automated arterial pressure measurement, and temperature measurement using a patient monitor (BSM-5135; Nihon Kohden Corp., Tokyo, Japan). Patients were breathing a fraction of inspired oxygen (F_IO₂) of 1.0 during the induction of general anaesthesia using remifentanil at a rate of 0.4–0.8 μg kg⁻¹ min⁻¹ and propofol via target-controlled infusion to a plasma concentration of 4 μg mL⁻¹. The lungs were ventilated manually via a face mask with an F_IO₂ of 1.0. Muscle paralysis was achieved with rocuronium 0.6 mg kg⁻¹ to facilitate the orotracheal intubation. Patients were intubated via a cuffed tracheal tube reinforced with a stylet with an internal diameter of 8.0 mm (Mallinckrodt™ endotracheal tube; Covidien plc., Dublin, Ireland). The lungs were ventilated mechanically through a ventilator (AVEA™ Ventilator Systems; CareFusion Inc., San Diego, CA, USA) with volume-controlled ventilation with an inspiratory pause of 10%, an inspiratory to expiratory ratio of 1:2, and a tidal volume (V_T) of 7 mL kg⁻¹ of the predicted body weight. The predicted body weight was calculated as 49.9 + 0.91 × [height (cm) − 152.4]. The respiratory rate (RR) was 12 bpm and varied to maintain eucapnia (end-tidal carbon dioxide partial pressure [EtCO₂] of 40–50 mmHg). Patients were ventilated using oxygen and air with an F_IO₂ of 0.5 as needed to maintain an oxygen saturation (SaO₂) ≥ 95%. PEEP was not initially added. An arterial cannula was inserted percutaneously into the radial artery of the non-dominant hand after the induction of anaesthesia, in line with the standard practice of our institution for continuous arterial pressure monitoring and blood gas sampling. An arterial blood gas analysis was performed within 1 min of sampling using a blood gas analyser (RAPIDLab^® 1200 Systems; Siemens Healthcare GmbH, Erlangen, Germany). Patients were placed in the horizontal lithotomy position. Anaesthesia was maintained with a continuous infusion of propofol, remifentanil, and rocuronium throughout the surgery. Adequate anaesthetic depth was maintained by bispectral index monitoring (Aspect A-2000™; Aspect Medical System, Inc., Newton, MA, USA). The infusion rate of propofol was varied to maintain the bispectral index in the range of 40–60. Maintenance of haemodynamic stability (arterial systolic pressure and heart rate 80–100% of the pre-anaesthetic value) included administration of remifentanil at a rate of 0.1–0.2 μg kg⁻¹ min⁻¹. The neuromuscular block was maintained with the administration of rocuronium at a rate of 0.4 mg kg⁻¹ h⁻¹. Standardised fluid management was performed in patients using a crystalloid solution (acetated Ringer’s solution; Terumo^®, Tokyo, Japan) at a rate of 20 mL kg⁻¹ h⁻¹ immediately before the anaesthetic induction and until the patient was placed in a steep Trendelenburg lithotomy position, followed by 5 kg⁻¹ h⁻¹ until the end of the surgery. The occurrence of intraoperative hypotension (mean arterial pressure < 65 mmHg or a decrease in mean arterial pressure > 20% of baseline for more than 5 min) was managed with a bolus of a 10 mL kg⁻¹ crystalloid solution with an incremental administration of intravenous vasoactive drugs (ephedrine 4 mg or phenylephrine 0.05 mg), as appropriate. To maintain normothermia, a heating blanket (Bair Hugger™; Augustine Medical Inc., Eden Prairie, MN, USA) and a blood and fluid warming system (Ranger™, Augustine Medical Inc.) were used, whereas no warmed infusions were used. Operating room temperatures were kept at approximately 23 °C (73.4 °F). During RARP, patients were in a steep Trendelenburg lithotomy position, a pneumoperitoneum was established with CO₂ insufflation, and the intra-abdominal pressure (IAP) was maintained automatically at 10 mmHg. At the end of the surgery, the infusions of propofol and remifentanil were discontinued and the residual neuromuscular paralysis was reversed with sugammadex 0.2-0.4 mg kg⁻¹.

Of the 24 screened patients, 19 patients were finally recruited, 2 patients who were not finally recruited (A time period from RARP0 to RALP5.2 was within 2 h) and 3 patients who refused to participate were excluded. So, this study was a relatively underpowered study. No other patients developed any complications perioperatively related to pneumoperitoneum, positioning, or anaesthesia during surgery. All surgeries were performed successfully without conversion to the open technique. The clinical characteristics of the enrolled patients are shown in Table 1; there were no significant intergroup differences. Respiratory and arterial blood gas analysis data are shown in Table 2.

In the C group, C_LUNG significantly decreased from pre-op to RARP0, RARP5.1 (P < 0.01), and RARP5.2 (P < 0.05) but did not significantly increase from RARP0 to RARP5.1 or RARP5.2. In the R group, C_LUNG significantly decreased from pre-op to RARP0 (P < 0.05) but did not significantly increase from RARP0 to RARP5.1 or RARP5.2. C_LUNG differed significantly between the two groups, at the same time point (RARP5.1 [P < 0.05] and RARP5.2 [P < 0.05]). PaO₂ did not significantly change from pre-op to RARP0 but significantly increased from pre-op to RARP5.1, RARP5.2, and post-op in the C group (P < 0.01). PaO₂ did not significantly change from pre-op to RARP0 and RARP5.1 but significantly increased from pre-op to RARP5.2 and post-op in the R group (P < 0.01). PaO₂ significantly increased from pneumo or RARP0 to RARP5.2 and post-op in the R group (P < 0.01). There were no statistically significant intergroup differences in PaO₂ during this procedure. PaCO₂ increased in both groups, but there were no statistically significant intergroup differences in PaCO₂ during this procedure.

Mean arterial pressure and heart rate remained stable through single RM that involved sustained inflation of 30 cmH₂O applied for 30 s at steep Trendelenburg lithotomy position. Intravenous vasoactive drugs (ephedrine 4 mg or phenylephrine 0.05 mg) had been administered only few bolus.

This small randomised clinical trial evaluated the effects of an RM of 30 cmH₂O applied for 30 s on the systemic oxygenation and C_LUNG of patients undergoing RARP. The main finding of our study was that an RM with PEEP during RARP was effective at improving C_LUNG. After PEEP 5 cmH₂O could be not sufficient to restore the atelectasis.

A pneumoperitoneum with CO₂ insufflation and steep Trendelenburg lithotomy position are used in combination to optimise the surgical view during RARP. A pneumoperitoneum with CO₂ insufflation can affect the cardiopulmonary system in several ways. Lung volumes decrease, mean arterial pressure increases, and CO₂ absorption can be associated with acidosis. All of these changes can lead to a wide range of cardiopulmonary distresses [16, 17]. During RARP, use of a steep Trendelenburg position is routinely requested by the surgeons to facilitate exposure of the pelvis and the lower abdomen causes the abdominal contents to push the diaphragm cephalad along with all of the mediastinal structures [18]. The diaphragm cranial shift by the abdominal contents and pneumoperitoneum may lead to an increased P_AW, reduce the lung’s functional residual capacity (FRC), decrease C_LUNG, predispose the patient to atelectasis, and aggravate a ventilation/perfusion mismatch [4]. C_LUNG is reduced, and this continues even after de-sufflation [19]. These pulmonary changes can have significant adverse consequences for patients with abnormal pulmonary mechanics. Maisch studied that the FRC revealed a plausible physiologic picture of the effects of PEEP or of PEEP in conjunction with an RM. At identical pressure levels, a larger FRC can be found after recruitment compared to the corresponding value before it. However, FRC seems unable to detect lung over-distension. Compared to the gain in PEEP before it, a gain in absolute lung volume (i.e., FRC) after recruitment cannot result from a pure distension of aerated alveoli or airways but must be the result of an increase in the number of functional alveolar units. Thus, this is proof of the intended “opening effects” of alveolar recruitment [9].

Several ventilation strategies aimed at improving arterial oxygenation and respiratory mechanics in patients undergoing laparoscopic surgery have been investigated in recent years. Studies have determined that the application of PEEP counterbalances the cranial shift of the diaphragm, thus increasing FRC and respiratory system compliance and reducing respiratory system elasticity [20]. Recent attempts have been made to translate the concept of LPV strategies from the context of adult respiratory distress syndrome [21]. The apparent success of mechanical ventilation based on a strategy of using the lowest PEEP results in acceptable oxygenation [22, 23]. The application of an “open lung” strategy consisting of an RM [24] followed by the subsequent application of PEEP has been suggested to effectively re-expand pneumoperitoneum-induced atelectasis and improve oxygenation in patients undergoing prolonged laparoscopic surgery [25]. In addition, given that the beneficial effects of a single RM is reportedly insufficient [26, 27], a recent clinical study suggested that the repetitive use of RM is a way to improve arterial oxygenation since it keeps the alveoli open and improves aeration [28]. A single application of 40 cmH₂O for 7–8 s was reportedly sufficient to prevent postoperative atelectasis after anaesthetic induction in patients with a normal body weight [29], and that an RM with a PEEP of 10 cmH₂O significantly improved their intraoperative pulmonary mechanics and oxygenation [9]. However, data on the use of an RM in surgical patients with healthy lungs, particularly those venti-lated with a protective ventilatory strategy, remain insufficient.

In patients who undergo laparoscopic surgery in the Trendelenburg position, an open lung strategy (recruiting pressure of 40 cmH₂O and PEEP 5 cmH₂O) applied after pneumoperitoneum induction increased transpulmonary pressure and led to alveolar recruitment and improved chest wall elasticity and gas exchange [30]. In the R group, an open lung strategy (sustained inflation of 30 cmH₂O for 30 s with a PEEP of 5 cmH₂O; mean TV of 7 mL kg⁻¹) applied after pneumoperitoneum in the Trendelenburg position improved C_LUNG but did not change PaO₂/F_IO₂ compared with patients in the C group. Compared with the practice of non-protective mechanical ventilation, the use of a lung-protective ventilation strategy (sustained inflation of 30 cmH₂O for 30 s with a PEEP of 6–8 cmH₂O; mean TV of 6.4 mL kg⁻¹) in patients undergoing major abdominal surgery was associated with improved clinical outcomes and reduced health care utilisation (IMPROVE ClinicalTrials.gov number NCT01282996) [1].

Andersson and colleagues found that the previously seen improvement in arterial oxygenation despite an increase in atelectasis volume could be due to an improved ventilation–perfusion matching during pneumoperitoneum [31]. This may cause ventilation/perfusion matching and maintain the PaO₂/F_IO₂ ratio. The Trendelenburg position decreased FRC, whereas 5 cmH₂O PEEP slightly recovered the ventilation/perfusion mismatch in the Trendelenburg position and could result in an increasing PaO₂/F_IO₂ ratio during surgery. A decremental PEEP trial identified a PEEP setting that sustained the oxygenation benefit of a 40 cmH₂O, 40 s lung-recruitment manoeuvre for 4 h [32]. Futier used each RM by applying a continuous positive airway pressure of 30 cmH₂O for 30 s [1]. With even larger inflation volumes, more than two repeated inflations to the same P_AW added little to the recruitment of normal lung tissue [24]. Repeated RM use may be necessary to improve the sustained C_LUNG [33].

Our investigation is under powered analysis to evaluate the effects of an RM in patients undergoing RARP and presents some limitations that require consideration. First, the latter value of PEEP could not be sufficient to restore the atelectasis in this study. Second, this study was limited by its small sample size. Therefore, although a single RM did not benefit the systemic oxygenation and C_LUNG of surgical patients undergoing RARP in the steep Trendelenburg lithotomy position with a pneumoperitoneum in our trial, this result is difficult to generalise. Third, the study was not conducted in a blinded fashion. The anaesthesiologist was aware of the mode of ventilation. Fourth, enrolled patients had an ASA Physical Status Classification score of 1–2; therefore, our results apply only to healthy patients. Finally, this study did not enrol patients with respiratory diseases or obesity (BMI ≥ 30 kg m⁻²), as these patients could be more vulnerable to the deterioration of oxygenation and respiratory mechanics during a pneumoperitoneum with CO₂ insufflation in a steep Trendelenburg lithotomy position.

In patients undergoing RARP, the addition of an RM effectively increased C_LUNG from the horizontal lithotomy position to a steep Trendelenburg lithotomy position under pneumoperitoneum. We suggest that by measuring P_OES to estimate P_{PLAT TP} and C_LUNG, mechanical ventilator settings could be more appropriately customised to accommodate interindividual variations in lung and chest wall mechanical characteristics.

This study showed promise for improvements in lung function, a topic that warrants further investigation. Further studies such as a large-scale multicentre studies or well-powered randomised controlled trials are required to more clearly determine the effects of a single RM and validate the use of RM with a lung protective ventilation strategy in patients undergoing RARP.