Surgical conditions in laparoscopic surgery are largely determined by the depth of neuromuscular relaxation during surgery. Especially in procedures that are confined to a narrow working field, such as retroperitoneal laparoscopic surgery (for example, renal and prostatic laparoscopic surgery), deep neuromuscular relaxation may be beneficial. Until recently, however, deep neuromuscular block (DNB, one or two twitches post-tetanic count (PTC)) came at the expense of a variety of issues that conflicted with its use. For example, occurrence of residual postoperative neuromuscular blockade after deep neuromuscular block (DNB) is a common adverse event (AE). Residual NMB is a risk factor for developing airway obstruction, hypoxia, and pulmonary complications, such pneumonia and atelectasis . The use of acetycholinesterase inhibitors, such as neostigmine, to reverse NMB, while beneficial, is relatively slow in onset of reversal. Furthermore, side effects due to acetylcholine-induced muscarine receptor stimulation are bradycardia, hypersalivation, nausea, and vomiting . Coadministration of a muscarine agonist, such as atropine or glycopyrrolate, is often necessary to counteract some of these side effects. These agents, however, in themselves may induce other side effects. Moreover, recent studies indicate that high-dose neostigmine (>5 mg) is associated with postoperative complications, including the need for reintubation and muscle weakness [3, 4].
Rapid, complete reversal of neuromuscular blockade was not possible until the discovery of sugammadex. Sugammadex is a modified γ-cyclodextrin. It was developed to selectively bind free plasma rocuronium, a nondepolarizing steroidal neuromuscular blocking agent . By binding free rocuronium, less rocuronium becomes available at the neuromuscular junction to bind to the muscarinic receptor . Nondepolarizing neuromuscular blocking agents (NMBAs), such as rocuronium, block the muscarine receptors at the neuromuscular junction, making them unavailable to acetylcholine-based signal transmission. Sugammadex has proven to reverse rocuronium-induced NMB rapidly [7–10]. Even high-dose rocuronium (1.2 mg/kg) and continuous rocuronium infusion used to achieve deep neuromuscular blockade can be reversed by sugammadex [11, 12].
Theoretically, the availability of sugammadex makes it possible to use DNB during surgery to improve surgical conditions without the occurrence of the above-mentioned AEs. The use of DNB to improve surgical conditions, however, has not yet been evaluated. This protocol was designed to study the relationship between the depth of NMB and the rating of the surgical conditions by the surgeon. To that end, either a deep NMB will be achieved with a rocuronium bolus administration followed by a continuous infusion (reaching 1–2 PTC) or a moderate NMB with a combination of an atracurium bolus administration and a mivacurium continuous infusion to obtain a level of NMB with a train-of-four (TOF) of 1 to 2. A combination of atracurium and mivacurium (two nondepolarizing NMBAs) is chosen, as they are part of the current anesthetic practice in our hospital for laparoscopic urological surgery. The deep block obtained with rocuronium will be reversed with sugammadex; the moderate block with neostigmine. During the laparoscopic procedure, the surgeon will rate the surgical conditions at 15 min intervals using a five-point surgical rating scale (SRS). To standardize the surgical rating, all surgeries are performed and rated by one surgeon with ample experience in the performed surgeries (RB).
A secondary aim of the study is to assess whether the anesthesiologist (the provider of the NMB and consequently responsible, in part, for the quality of the surgical conditions) is able to quantify the surgical field in surgical terms and also to assess whether the surgeon and anesthesiologist agree in perception or whether there is a disconnect in the opinions of surgical conditions between the two. This is important, as the request of surgeon for additional neuromuscular blockade is often not well received by the anesthesiologists (especially not at the end of the case) owing to concerns for residual NMB and other postoperative complications. To this end, video images of the intra-abdominal part of surgery are captured and rated (using the SRS) by five anesthesiologists and ten surgical experts, who serve as a control group.
Additional secondary endpoints of the study include the effect of depth of NMB on economic parameters (time to optimal extubation conditions (TOF 4 with T1/T4 ratio >90%), time to extubation, duration of surgery, and time in the post-anesthesia care unit), perioperative hemodynamics, and postoperative conditions (respiratory rate, arterial oxygen saturation, pain, sedation).
We hypothesize that:
There is a positive association between the depth of NMB and the surgical condition as rated by the attending surgeon.
There is a disconnect between the perception of the surgeon and the anesthesiologist in the rating of the surgical conditions.
Reversal of a deep NMB with sugammadex leads to postoperative conditions similar or superior to the conditions obtained from reversal of a moderate NMB with neostigmine.