1997 OPEN FORUM Abstracts
'Prolonged Weakness following Neuromuscular Blockade: Etiology and Prevention'
John W. Hoyt, M.D., Sunday, December 7, 1997.
Neuromuscular blocking agents (NMBAs) or muscle relaxants are common medications used by anesthesiologists in the operating room to facilitate surgery and, from time to time, by intensivists in the critical care unit to facilitate mechanical ventilation. NMBA and not muscle relaxant is the preferred term for these pharmacologic agents that are nondepolarizing, competitive inhibitors of the acetylcholine receptor on skeletal muscle. From time to time physicians will prescribe a benzodiazepine or other sedative agent to patients with back pain and describe the medication as a "muscle relaxant". That has lead to great confusion about the sedative properties of a NMBA which are in fact completely free of all sedative and analgesic properties.
In the early days of mechanical ventilation and critical care, 1960-1970, NMBAs were used commonly in the intensive care unit (ICU) to aid in the use of control mechanical ventilation (CMV) with a volume limited ventilator. Morphine was administered to the patient intravenously to provide sedation and analgesia and the patient was paralyzed with curare to obtain complete cooperation with the ventilator. The ventilator circuit for CMV did not permit spontaneous ventilation so various attempts were made by the clinician to reduce or eliminate patient breathing that was out of synchrony with the ventilator.
The 1970 era of critical care heralded in partial ventilatory support where patient respiratory effort was desirable and the use of NMBA was thus undesirable. Assisted mechanical ventilation (AMV) and even more important intermittent mandatory ventilation (IMV) required patient effort to bare part of the load of the minute ventilation. IMV for the first time in the ICU permitted spontaneous ventilation on a ventilator circuit between mechanical breaths thus eliminating any interest by the clinician in paralyzing the patient. In fact even sedation and analgesia were minimized to maintain patient sensitivity to carbon dioxide, preserving respiratory drive.
In the late 1980s and early 1990s there was in critical care a resurgence of interest in paralyzing patients with a NMBA. This was driven by a desire to use new forms of respiratory support such as pressure control ventilation (PCV) and pressure control inverse ration ventilation (PCIRV) which is less well tolerated in the awake patient than IMV. PCV and PCIRV use small tidal volumes, 6-8 ml./kg.; low peak airway pressures, less than 40 cm. H20; long inspiratory times, 40% or greater such that the inspiratory/expiratory (I/E) ratio may be less than 1; and often permit hypercarbia. All of these factors usually require substantially more sedation, analgesia, and neuromuscular blockade than any form of ventilation since the CMV era of the 1960's.
The change in forms of ventilation was driven by a concern among intensivists that traditional tidal volumes, 12-15 ml./kg. and high peak airway pressures traumatized the lung and increased the mortality of respiratory failure. These concerns were particularly relevant to Adult Respiratory Distress Syndrome (ARDS). First identified in the late 1960's in Viet Nam, ARDS was a particularly lethal form of respiratory failure. Early mortality rates recorded in Viet Nam on pressure limited ventilators were in excess of 70%. The use of volume limited ventilators and positive end expiratory pressure (PEEP) in the early 1970's seems to have reduced this mortality rate to about 50% with some variation depending on the etiology of ARDS, pulmonary contusion versus sepsis to give an example of a low mortality etiology versus a high mortality etiology.
As intensivists began to focus on "volutrauma", the name attached to the alleged increase in ARDS mortality from high tidal volumes and possibly high airway pressures, they had to reach back into the history of critical care to the CMV era. They brought forth the use of NMBA agents and heavy sedation to facilitate PCV and PCIRV. To date it is not clear from the medical literature that these new techniques are any better than older forms of mechanical ventilation. In addition there are now substantial concerns about the safe use of NMBAs in critically ill patients.
Concerns over the safety of NMBAs in critical care reached fevered pitch in the late summer and early fall of 1992. In that year Segredo published an article in the New England Journal of Medicine (NEJM) on prolonged paralysis after the use of vecuronium (steroid nucleus NMBA) to facilitate mechanical ventilation in seven patients in a medical intensive care unit. Paralysis persisted for 6-168 hours after the administration of vecuronium was discontinued. In the case of 168 hours, the patient succumbed to the primary illness before there was return of muscle activity. This paper highlighted concerns over using these agents in patients with renal failure noting in addition that four of the seven patients had liver failure. The authors made a case for delayed clearance of the drug in the face of renal and liver insufficiency.
AARC 50th Anniversary, December 6 - 9, 1997, New Orleans, Louisiana.