The purpose of this specific study is to compare the neuromuscular block reversal rates and effects for sugammadex, a selective relaxant binding agent, with neostigmine. In many types of surgery, there appears to be a benefit for the patient to be kept in a state of profound relaxation throughout the entire procedure. Anesthesiologists are usually hindered in this goal through the surgery in its entirety because of the inability of standard agents to rapidly reverse such profound neuromuscular block.
This forces anesthesiologists to restrict the level of neuromuscular block near the end of surgery (Lemmens, El-Orbany, Berry & Martin, 2010). Since sugammadex has the potential to decrease the time necessary to reduce neuromuscular block, there is an opportunity for it to aid anesthesiologists by allowing them to extend the duration of the profound relaxation later into a procedure. This study was built around the framework that sugammadex has been shown to successfully reverse rocuronium induced profound blocks to a train of four ration of .
9 relatively quickly. The concept of interest here, then, is whether or not these properties of sugammadex can translate into faster block reversals when using vecuronium, which is more potent than rocuronium (Lemmens, El-Orbany, Berry & Martin, 2010). Furthermore, the conceptual interest includes the existence of any serious adverse effects in doing so. The sample size was ninety-four patients spread randomly across eight centers in the United States. Originally it was planned that fifty-two patients receive sugammadex and the rest receive neostigmine.
The population consisted of adults with American Society of Anesthesiologist (ASA) class I-IV receiving general endotracheal anesthesia for elective surgery requiring neuromuscular blockade both for induction and maintenance. They were further limited to general surgery in the supine position. Patients were excluded if they had a neuromuscular condition, history of malignant hyperthermia, significant renal dysfunction, an allergy to narcotics, muscle relaxants or other medications used during general anesthesia. Exclusions also included pregnant and breastfeeding women and
women who were of childbearing age and not under adequate birth control. The sample size was further reduced when it was determined by the data and safety board discontinued the neostigmine group due to the marked difference in efficacy. There was also one instance of a patient receiving rocuronium instead of vecuronium. The final sample size was forty-six patients receiving sugammadex and thirty-six receiving neostigmine. The sample size does appear to be representative of the general population in terms that it was conducted throughout the United States and that the population was more female.
There were several biases in the sampling method, in terms of limiting the patient population in terms of comorbidities, allergies, and limiting the procedures to general elective surgery. Another bias was the limitation of only using vecuronium and sevoflurane. This was a phase III safety-assessor blinded study across several different institutions utilizing the same procedures. The procedure was to place Train-of-Four (TOF) monitor on the arm at the ulnar nerve with a transducer affixed to the volar aspect of the distal phalanx of the thumb.
This was placed on the arm that contained the intravenous line for drug delivery and calibrated in the operating room. The TOF was to have repetitive stimulation every fifteen seconds at the ulnar nerve until the end of anesthesia or at least until the TOF ratio was 0. 9. There were no variables actively defined in the article except to point out that the same procedure was used to minimize variability. This being there is variability because TOF interpretation is very subjective. In this study the attending anesthesiologist determined when spontaneous recovery had been achieved and then the reversal was given.
This opens up to each anesthesiologist having their own subjective opinion on spontaneous recovery leading to at different levels of blockade that reversal was administered. The data was collected through times based upon when reversal was given to complete recovery in which the TOF was 0. 9. They also recorded the TOF measurements from the TOF monitor itself. This method of measuring times is reliable in that the researchers followed the same protocol for each case. Any case that they deemed to have broken protocols they eliminated and reported why.
The results were overwhelmingly in favor or Sugammadex as the superior reversal for muscle relaxant. The TOF recovery for Sugammadex was fifteen-fold faster than that of Neostigmine. With an average time to TOF recovery of 0. 9 in Sugammadex at 4. 5 minutes and Neostigmine at 66. 3 minutes. Based on research done in this area it seems to be very consistent. A study on Residual neuromuscular blockade at extubation, conducted by Daniel Sabo, et al, came to the same conclusions. They concluded that not only did Sugammadex work quicker than Neostigmine, but it was also more superior in terms preventing residual blockade.
Though the research done here is limited to approximately 80 participants, the results are very profound. Currently the practice of utilization of non-depolarizing neuromuscular blockers for general surgery consists of an initial bolus which results in the complete blockade of nicotinic receptors and full muscular paralysis. Time is then allotted for the medication to subside while peripheral nerve stimulator is used to assess the degree of block in the patient. Patients are generally allowed to return to a train of four of 1-2/4 and maintained with smaller incremental doses of NDMR.
This level results in approximately 80 to 90% blockade. According to Morgan, Mikhail, & Murray, as the surgery nears end, patients are often passively returned to a TO4 of 3-4/4, or 0 to 75% blockade in anticipation of surgical end and reversal need (2006). At this time, the patient is at a much higher risk for movement which may affect the surgical field adversely. Because current practice requires a minimal of 1/4 TO4 to safely reverse NDMR with Neostigmine, patients are placed at risk. The use of Sugammadex allows the practitioner to reverse the NDMR at a much deeper level to a safe level of return of neuromuscular function.
This added feature would allow practitioners to carry their patients at much deeper levels of blockade and decrease the risk of movement near procedure end time, without adding lengthy emergence time to the surgery. The results of this research are very promising towards the adaptation and acceptance of Sugammadex for reversal of NDMR. The 15-fold faster time to recovery of train of 4 that was found in the Sugammadex group could have large implications for current anesthesia practice (Lemmens et al. , 2010).
For future research, recommendations would include limiting the study to a younger and healthier population. Also limiting the study to more specific surgical procedure such as laparoscopic cases. Tighter control needs to be made on single use of volatile agent. And finally, consider the research taking place at a single location to reduce subjectivity and cultural differences in practice as well as limiting potential regional variance in the population participating. A final control could be done by limiting the time of administration more exactly to a post tetanic count of 1 – 2.
This would provide a more equivalent level of blockade prior to administration. There are multiple limitations found in this study. The researchers attempted to limit many factors in differences in research participants. Lemmens et al. explain, exclusions were made for patients with neuromuscular disorders, history of malignant hyperthermia, renal insufficiency, pregnancy, breast feeding , or allergies to narcotics, muscle relaxants (2010). The study also limits to use of Sevoflurane, however, a few of the participants received Isoflurane or Desflurane instead.
Other notable differences in the populations studied include varying surgical procedures, varying overall current health of the patients as indicated by ASA classification, use of nitrous oxide in some cases, and age. Of most significant of these variables, age and current health can have profound impacts on recovery time from anesthetic agents due to changes in physiological processes including but not limited to decreased cardiac output and decreased renal function at a subclinical level. Nagelhout & Plaus explain, human organ function declines at a rate of approximately 1% for each year over age 30 (2010).
Also, the study was performed at multiple clinical sites which can add bias by way of subjectivity and serve to decrease the validity to the findings. References Lemmens, H. J. , El-Orbany, M. I. , Berry, J. , & Martin, G. (2010). Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine. . BMC Anesthesiology, 10(15), doi: 10. 1186/1471-2253-10-15 Morgan, G. E. , Mikhail, M. S. , & Murray, M. J. (2006). Clinical anesthesiology (4thed. ). New York: McGraw-Hill. Nagelhout, J. J. , & Plaus, K. L. (2010). Nurse anesthesia (4th ed. ). St. Louis,MO: ElsevierSaunders.