RSI

[ffmedic9588]

Connie I hope that our new medical director might entertain the thought of RSI. I believe we could be very successful at it. My personal opinion why our success rate is low now is because if you document correctly each time the blade is placed even for FBR it is considered a failed attempt. And also I think we need more choices of meds. What is the success rate elsewhere for RSI and regular ETI???

[Ace844]

(Heart & Lung: The Journal of Acute and Critical Care

Volume 35 @ Issue 3 , May-June 2006, Pages 178-189

doi:10.1016/j.hrtlng.2005.08.003

Copyright © 2006 Mosby, Inc. All rights reserved.

Issues in pulmonary nursing

Functional recovery after neuromuscular blockade in mechanically ventilated critically ill patients

Janet G. Whetstone Foster PhD, RN, CNS, CCRNa, and Angela P. Clark PhD, RN, CS, FAAN, FAHAb

aTexas Woman’s University, Houston, Texas

bThe University of Texas at Austin, Austin, Texas.

Available online 18 May 2006)

Background

An estimated 24% to 70% of individuals have prolonged paralysis or severe weakness after receiving neuromuscular blocking agents (NMBAs) when therapy is terminated.

Objectives

The purposes of this study were to (1) evaluate the relationship between recovery of neuromuscular transmission (NMT) and functional muscle activity after NMBA administration; (2) evaluate the relationship between delayed recovery of NMT or muscle activity and functional performance; and (3) determine the predictors of delayed recovery of NMT, muscle activity, and functional performance.

Methods

This was a multisite study using a prospective, nonexperimental, descriptive design with convenience sampling techniques. Instruments used included a five-point muscle score, Actigraph, and peripheral nerve stimulator.

Results

Key findings were as follows: (1) NMT returned promptly, whereas muscle activity remained severely depressed; (2) only two subjects (5%) recovered functional performance within 24 hours; (3) degree of muscle weakness immediately after neuromuscular blockade was associated with prolonged time to extubation and mobility; and (4) predictors of delayed recovery included cumulative dose of aminosteroid NMBAs, age, and renal function.

Conclusion

Prolonged recovery of muscle activity and extreme weakness may occur despite brisk recovery of NMT after neuromuscular blockade.

Neuromuscular blocking agents (NMBAs) are most commonly administered to critically ill patients to decrease the work of breathing and facilitate mechanical ventilation for acute lung injury, and for management of intracranial pressure, control of muscle spasms associated with tetanus, drug overdose, seizures, and preservation of delicate reconstructive surgery.1 NMBAs paralyze all skeletal muscle with little effect on smooth, cardiac, or ocular muscles. An undesirable effect of the drugs recognized for more than two decades is prolonged paralysis and severe weakness after termination of NMBA therapy.1, 2 and 3 Spontaneous resumption of voluntary movement, according to previous studies, should occur in less than 4 hours after concluding therapy with NMBAs.4 However, there are reports of patients remaining paralyzed or acutely weak for hours, days, and even months. Persistent paralysis or severe weakness after termination of NMBAs has been estimated as high as 24% to 70%.5, 6 and 7

Background

Numerous terms have been used to describe the prolonged neuromuscular complications of NMBAs including acute quadriplegic myopathy syndrome (AQMS), floppy man syndrome, critical illness polyneuropathy (CIP), and acute myopathy.1, 8 and 9 Regardless of the term used, profound immobility results, causing exaggerated skeletal muscle atrophy and functional alterations in every major organ system. Health care costs increase exponentially when patients remain paralyzed or significantly weak, because this perpetuates ventilator dependence and costly related care, prolonged use of intensive and acute care services, and comprehensive physical and pulmonary rehabilitation.

Two patterns of weakness after discontinuation of NMBAs have been identified. One is prolonged recovery time of 50% to 100% longer than predicted determined by pharmacologic parameters such as duration of action and accumulation of metabolites, generally lasting a period of hours. The second pattern, AQMS, is devastating diffuse weakness persisting for days or weeks long after termination of NMBAs and is characterized by abnormal electromyography and muscle biopsy findings, along with slight elevations in serum creatine phosphokinase.1 Cranial nerve function and sensation remain intact.

Monitoring the neuromuscular twitch response with a peripheral nerve stimulator during NMBA therapy for medication titration is recommended, which should limit drug overdosage and prevent prolonged drug effects.1 Lower cumulative doses of NMBAs and faster recovery of neuromuscular transmission (NMT) have been demonstrated when doses are titrated according to peripheral nerve monitoring, but no improvement in functional muscle activity has been reported.4 Moreover, the muscle response to peripheral nerve stimulation is merely a twitch and therefore severe muscle weakness is often present even when NMT recovers. No studies have evaluated the relationship between return of NMT and resumption of functional muscle activity. The purposes of this study were to (1) evaluate the relationship between recovery of NMT and functional muscle activity when peripheral nerve monitoring is performed during NMBA administration; (2) evaluate the relationship between delayed recovery of NMT or muscle activity and functional performance; and (3) determine the predictors of delayed recovery of NMT, muscle activity, and functional performance.

The nervous system

The two principal divisions of the nervous system include the central nervous system (CNS) and peripheral nervous system (PNS). The CNS consists of the brain and spinal cord, whereas the PNS is composed of the sense organs and nerves. Twelve pairs of cranial nerves and 31 pairs of spinal nerves link the brain, spinal cord, sense organs, and muscles, facilitating communication between the CNS and PNS. The PNS is further subdivided into the autonomic division, which is concerned with internal regulatory mechanisms and functions involuntarily, and the somatic division, which includes the sense organs, sensory neurons, and motor neurons and controls responses to external stimuli.10

Voluntary movement involves neuronal structures in both the CNS and PNS through the upper and lower motor neurons. The upper motor neuron originates in the motor cortex of the brain, with the nerve axons forming the corticospinal tract of the spinal cord. Here, the neurons synapse with the lower motor neurons of the spinal cord that directly innervate skeletal muscle. Voluntary muscle activity and coordination is achieved through complex neuronal interaction and coordination between the premotor cortex, primary motor cortex, basal ganglia, and cerebellum in the brain, corticospinal tracts in the brain stem and spinal cord, and terminating at the motor neuron endplate as it connects to the skeletal muscle.10 NMBAs primarily affect the PNS at the synaptic cleft between the motor neuron and muscle fiber, rendering diminished or absent muscle activity.

The reticular activating system in the brain stem is responsible for maintaining consciousness and determines state of alertness. In contrast with NMBAs, sedatives, hypnotics, anxiolytics, and narcotic analgesics used in conjunction with NMBAs alter motor responses to external stimuli through depressing effects on the reticular activating system, basal ganglia, and other structures in the brain in the CNS.11

Neuromuscular blocking agents

NMBAs exert their primary effects at the neuromuscular junction (NMJ) of the motor neuron of striated muscles by interfering with the release or the action of the neurotransmitter, acetylcholine.12 Nondepolarizing agents, used most commonly in the critically ill, prevent NMT by competing with acetylcholine at the receptor sites on the postsynaptic terminal. This prevents activation of acetylcholine, which in turn, prevents depolarization, contraction, and muscle movement.10 Two classes of nondepolarizing agents are used clinically, the aminosteroid derivatives and the benzylisoquinolinium derivatives. The most commonly used aminosteroid derivatives in the intensive care unit (ICU) include pancuronium and vecuronium.13 and 14 Of the benzylisoquinolinium compounds, atracurium and cisatracurium are used most often.13

Although the effects on the NMJ are similar among agents in the two groups of nondepolarizing agents, metabolism and elimination processes differ. The aminosteroids are eliminated through both renal and hepatic pathways. Metabolism of pancuronium and vecuronium produce active metabolites, which have approximately 80% of the neuromuscular blocking effects of the parent drugs.15 Atracurium and cisatracurium, in contrast, are largely cleared by a process called Hofmann degradation, a mechanism in which the drugs are nearly spontaneously reduced to less complex compounds at physiologic pH and temperature to two molecules, laudanosine and acrylate, and that is independent of organ function and enzyme action.16 However, when the benzylisoquinolinium compounds are substituted for aminosteroid derivatives for patients with compromised renal or hepatic function, prolonged paralysis, and persistent weakness have been reported.1 and 17

Medications and conditions that potentiate paralysis or weakness

Residual effects of NMBAs have been associated with duration of NMBA administration, concomitant use of aminoglycosides and corticosteroids, renal failure, and electrolyte and acid-base imbalance.1, 18, 19, 20, 21 and 22 Short-term delay in recovery of neuromuscular activity, evident in hours to days after termination of NMBAs, most likely results from slow return of NMT. This may be attributed to prolonged blockade at the NMJ resulting from accumulation of NMBAs or metabolites, or excess dose or duration of NMBA infusion. Aminoglycosides and several other medications act synergistically with NMBAs, interfering with impulse transmission at the NMJ and may cause delayed recovery Table I.21

Table I.

Drugs and conditions that potentiate neuromuscular blocking agents17 and 19 Aminoglycosides

Amikacin

Gentamicin

Neomycin

Streptomycin

Tobramycin

Other antibiotics

Clindamycin

Kanamycin

Polymixin A,B,E

Lincomycine

Tetracyclines

Vancomycin

Procaine

Other drugs

Beta-blocking agents

Calcium channel blockers

Cyclosporine

Dantrolene

Diuretics

Magnesium sulfate

Nitroglycerin

Procainamide

Quinidine

Trimethaphan

Sedatives/psychotropics

Benzodiazepines

Etomidate

Droperidol

Ketamine

Lithium carbonate

Midazolam

Local anesthetics

Bupivacaine

Lidocaine

Mepivicaine

Prilocaine

Volatile inhalational anesthetics

Enflurane

Halothane

Isoflurane

Electrolytes/acid-base

Acidosis

Hypocalcemia

Hypokalemia

Hypermagnesemia

Hypothermia

Renal failure, possibly because aminosteroid NMBAs depend largely on renal excretion, has been associated with prolonged paralysis and persistent weakness. High concentrations of metabolites of vecuronium and pancuronium have been reported in patients with renal failure who exhibit residual drug effects.20 Continued circulation of the metabolites prolongs exposure of nerve receptors to neuromuscular blockade and may account for prolonged paralysis.20 Acid-base and electrolyte abnormalities may cause failure of transmitter release, interfere with receptor/transmitter union, or disrupt ion channels, hindering impulse spread throughout the NMJ.18

The second pattern of neuromuscular dysfunction, weakness that persists for weeks to months, has been linked with steroid use and the development of a myopathic process.22 Corticosteroids do not directly interfere with impulse transmission at the neuronal portion of the NMJ. Instead, corticosteroids cause direct muscle tissue damage. Atrophy, necrosis, architectural disarray, myosin loss with degeneration of fibers, lipid accumulation, and multiple metabolic alterations can occur.1 and 23 These structural and functional variations account for disruption in muscle function. The molecular structure of aminosteroidal compounds, vecuronium and pancuronium, is similar to that of corticosteroids. Concurrent administration of corticosteroids and vecuronium or pancuronium may precipitate muscle fiber degeneration, resulting in AQMS.1

Methods

This was a multisite study using a prospective, nonexperimental design. Data collection took place over a 20-month period in four critical care units in three large metropolitan medical center facilities. The study was approved by the institutional review boards at the designated institutions, and informed consent was obtained from the patient’s next of kin before enrollment into the study.

A convenience sampling technique was used. On notification of the primary investigator at the time NMBAs were initiated, subjects were screened for eligibility criteria and entered into the study if the family consented. Subject eligibility included age 18 years or older, endotracheal intubation, supported by mechanical ventilation, and receiving NMBAs as a continuous infusion for more than 24 hours. Demographic information was collected from the medical record, and Acute Physiology and Chronic Health Evaluation scores (APACHE III) were calculated. Medications administered in the ICU and results of laboratory tests, including serum electrolytes, renal and liver function tests, and arterial blood gases, were recorded. Exclusion criteria included a diagnosis of underlying neuromuscular disease, brain injury, spinal cord injury, history of previous sensitivity to NMBAs, and pregnancy. Subjects hospitalized for traumatic injury were screened for brain injury before initiation of NMBAs, because injury to upper motor neurons or depressed level of consciousness could explain delayed recovery of muscle activity. Physical examinations were conducted to assess for movement of extremities and response to verbal commands. Subjects with Glasgow coma scores below 10/15 were excluded; only compromised verbal scores as the result of intubation were acceptable.

Data were collected by the primary investigator with the assistance of designated critical care nurses who received initial and ongoing training. The training was provided by the primary investigator and included data-collection procedures, subject eligibility, and validation of proper application of the instruments. Recovery data were calculated from the time NMBAs were discontinued and included time to recovery of muscle activity, functional performance, endotracheal extubation, mobility, and NMT.

Recovery of muscle activity was measured with two instruments: (1) a widely used five-point scoring system that evaluates the force of primary muscle groups against gravity and resistance24 and (2) actigraphy, which senses and records movement detection and vigor over time. The number of hours within the first 24-hour time frame after discontinuance of NMBAs to achieve the best muscle activity score was entered as the muscle activity recovery time. Table II shows scoring criteria.

Table II.

Muscle scoring system (Medical Research Council, 1976)22 No movement or contraction = 0

Palpable contraction, no movement observed = 1

Movement at the joint with gravity eliminated = 2

Able to move the joint against gravity = 3

Able to move the joint against resistance, less than normal = 4

Fully normal strength = 5

The Actigraph selected for this study was the Actiwatch,™ (Minimitter Company Inc., Sun River, OR), which is a wrist-worn, coin battery-operated device weighing approximately 3 ounces. The sensor uses a piezoelectric element that senses movement and translates it to an electrical signal, which is continuously sampled by a microprocessor and stored in memory.25 Validity, reliability, and sensitivity have been well established in the laboratory25 and in clinical research to discriminate between sedentary and nonsedentary activities.26 Three Actigraph measurements were recorded: total average activity counts over the first 24 hours after termination of NMBAs, average activity counts within the first 4 hours, and average activity counts within the 20- to 24-hour interval after NMBAs were discontinued.

Functional performance, defined as volitional movement necessary for activities such as repositioning, suctioning, and communication gestures commonly used by intubated patients, was determined through direct observation by the primary investigator 20 to 24 hours after NMBA termination. The 24-hour time frame for measurement was selected because it allows for reasonable recovery time from neuromuscular blockade based on pharmacologic parameters while minimizing the effects of prolonged bedrest and immobilization. Time to extubation and time to mobility, defined as ambulation or transfer to a chair, was calculated in number of days after NMBA termination and was determined by retrospective medical record review.

NMT was measured with a peripheral nerve stimulator, the Microstim Plus P/N 7100 (Neurotechnology, Inc. Kerrville, TX). The instrument has been calibrated against a standardized delivery of milliamperes at the National Bureau of Standards, Washington, DC, to ensure instrument sensitivity and accuracy in the delivery of stimulating current indicated by the milliamperes selector dial. The ulnar nerve and adductor pollicis muscle were used to test the train-of-four (TOF) response to peripheral nerve stimulation in most instances, with a few subjects’ clinical condition necessitating use of the facial nerve and orbicularis oculi muscle for testing. At the conclusion of NMBA administration, the TOF response was measured hourly until four twitches resumed.

All of the subjects’ medications from admission to the ICU to 24 hours after discontinuing NMBAs were assessed. Drugs known to act synergistically with NMBAs on the NMJ were recorded. Corticosteroids, sedatives, and other drugs that may influence recovery from neuromuscular blockade were recorded. Table III shows a list of medications for each subject.

Table III.

Medications received by subjects that may potentiate the affect of continous neuromuscular blocking agent infusion Study ID Drugs that potentiate NMBAs Sedatives Corticosteroids

1 Mannitol, magnesium Propofol,† morphine, lorazepam, pentobarbital

2 Mannitol, tobramycin, magnesium, vancomycin, furosemide, nicardipine Propofol, morphine, lorazepam, fentanyl

3 Nicardipine, magnesium, labetolol, magnesium, diamox Propofol, lorazepam, haloperidol

4 Magnesium, tobramycin Propofol, lorazepam, haloperidol Hydrocortisone

5 Pancuronium⁎ Lorazepam, morphine, general anesthesia

6 Mannitol, esmolol, rocuronium⁎ Propofol, morphine

7 Rocuronium,⁎ furosemide, magnesium, clindamycin, vancomycin Propofol, lorazepam, haloperidol, fentanyl, morphine

8 Rocuronium,⁎ magnesium, clindamycin, mannitol Propofol, morphine, lorazepam, pentobarbital

9 Nimodipine, labetolol, tobramycin, rocuronium⁎ Propofol, morphine

10 Methylprednisolone

11

12 Furosemide, clindamycin, rocuronium,⁎ cisatracurium,⁎ vancomycin, midazolam Propofol, lorazepam, morphine, fentanyl Methylprednisolone

13 Lorazepam, morphine

14 Magnesium, labetolol Lorazepam, morphine

15 Furosemide, rocuronium,⁎ vancomycin, midazolam, nicardipine, magnesium, labetolol, nitroglycerin, cyclosporine Propofol, morphine, lorazepam Prednisone, hydrocortisone

16 Magnesium Morphine, lorazepam

17 Mannitol, magnesium, gentamycin Morphine, lorazepam

18 Furosemide, clindamycin, vancomycin, vecuronium,⁎ magnesium, midazolam Propofol, lorazepam, morphine

19 Lorazepam, morphine

20 Vancomycin, magnesium, furosemide, midazolam Propofol, morphine, lorazepam Methylprednisolone

21 Magnesium, vancomycin Lorazepam, propofol

22

23 Vancomycin, furosemide, magnesium, midazolam Lorazepam, morphine, propofol, fentanyl

24 Vancomycin Lorazepam, propofol

25 Vecuronium, pancuronium,⁎ midazolam, magnesium, gentamycin, labetolol, gentamycin Morphine, lorazepam, propofol, midazolam, haloperidol

26 Vancomycin, gentamycin, magnesium, labetolol, metaprolol Morphine, lorazepam

27 Magnesium, labetolol Morphine, lorazepam

28 Propofol, lorazepam, haloperidol

29 Magnesium, clindamycin, vecuronium,⁎ metoprolol Propofol, morphine, lorazepam

30 Magnesium, calcium Morphine, lorazepam

31 Diltiazem, vecuronium,⁎ metoprolol Propofol, morphine, lorazepam Methylprednisolone

NMBA, Neuromuscular blocking agent.

⁎ Bolus doses administered before continuous infusion.

† Propofol is a sedative-hypnotic agent used for induction and maintenance of anesthesia or sedation.

Data analysis

Statistical analyses included descriptive statistics, chi-square analysis, bivariate analysis, Spearman rho correlation, and linear regression analysis. Linear regression analysis was run using five separate analyses with all indices of recovery except time to return of muscle score serving as dependent variables.

All baseline data and TOF responses were entered and stored on a PC data-collection program for subsequent analysis, using SPSS 10.0 Software (SPSS Inc., 1999).27 Stored data in the Actigraph were downloaded to an IBM-compatible microcomputer (IBM, Armonk, NY) for interpretation and analysis.

Results

Thirty-seven subjects were entered into the study; however, subject mortality left 31 subjects remaining for analysis. Four subjects expired while receiving NMBAs; thus, there were no recovery data for analysis, and two subjects failed eligibility criteria after enrollment. The sample was composed of white non-Hispanic (41.9%), Hispanic (35.4%), and black non-Hispanic (22.5%). A summary of the subjects’ gender, age, and medical diagnoses is shown in Table IV. The median APACHE score was 52.59 (M = 54.63, standard deviation [sD] = 20.24, range 83). Length of hospital stay ranged from 9 to 120 days, with a median of 37 days (M = 42.67, SD = 27.92). Range of ICU length of stay was 7 to 60 days, with a median of 26 days (M = 29.06, SD = 16.76). Subjects had one to six medical diagnoses. Subjects received from one to nine medications known to potentiate blockade (n = 27, median 4, M = 3.8, SD = 2.0). The number of sedatives, which could reduce the level of consciousness and thereby influence activity, ranged from 2 to 5 (n = 30, median 3, M = 2.83, SD = .95), with 20 subjects receiving propofol, primarily during NMBA administration. Nine subjects received propofol for 1 day only, six subjects received propofol for 2 days, three subjects received propofol for 3 days, one subject received propofol for 5 days, and one subject received propofol for 8 days concurrently with NMBAs. Two subjects had propofol initiated during the 4 hours immediately after termination of NMBAs, but it was discontinued before the 20- to 24-hour period. In addition, two other subjects had propofol initiated during the 20- to 24-hour period after NMBAs were discontinued. Six subjects received corticosteroids.

Table IV.

Subject age, race, and medical diagnoses Age (y) Medical diagnoses

M 25 SDH, SAH, craniotomy, pneumonia

M 26 MVA, skull frx, DAI

M 87 HTN, Lt basal ganglia, SAH

MVA, cardiac tamponade, pericardial window, frx rt acetabulum,

M 40 ARDS, ARF

MVA, fetal demise, hysterectomy, nephrectomy, splenectomy, multiple

F 29 frx

M 24 MVA, CHI, SAH, ICH, multiple frxs

F 45 AMI, ARDS, aspiration pneumonia

M 18 MVA, CHI, pulmonary contusion, acute respiratory failure, ARF

M 40 SAH

F 43 Asthma, pneumonia

M 18 MVA, pulmonary contusion, ARF, acute respiratory failure

M 48 pneumonia, ARDS

M 19 MVA, ARDS

MVA, exploratory laparotomy, splenectomy, ARDS, subtotal

M 50 pancreatectomy

M 36 S/P renal transplant, ACDF, ARDS, pneumonia

M 49 MVA-pedestrian, frx pelvis, frx rt femur, pneumothorax

M 18 Fall, SDH, epidural hematoma

M 43 ETOH withdrawal, cirrhosis, ARDS

M 19 MVA, pelvic frxs

F 33 Pneumonia, sepsis, ARF, pneumothorax, hepatic insufficiency

F 41 Hemoptysis, metastatic lung cancer, S/P TB

F 34 Lupus, CRF, bleeding rt femoral artery

M 48 Cirrhosis, esophageal varices, UGI bleed, ARDS, sepsis, DIC

F 34 DM, CHF, pleural effusion

M 20 PE, multiple gunshot wounds, lobectomy, cholecystectomy

M 41 MVA, frx C5-C4, fixation and stabilization

M 18 MVA, rib frxs, liver laceration

M 54 Hemoptysis, S/P TB

F 23 MVA, femur rt femur, pulmonary embolism, ARDS

M 43 MVA, pelvic frx, lt tibia/fibula frx

F 34 Nephritis, Lupus, ICH, pulmonary hemorrhage

SDH, Subdural hemorrhage; SAH, subarachnoid hemorrhage; MVA, motor vehicle accident; frx, fracture; DAI, diffuse axonal injury; HTN, hypertension; lt, left; rt, right; ARDS, acute respiratory distress syndrome; ARF, acute renal failure; CHI, closed head injury; ICH, intracerebral hemorrhage; AMI, acute myocardial infarction; S/P, status post; ACDF, anterior cervical disc fusion; ETOH, alcohol; TB, tuberculosis; CRF, chronic renal failure; UGI, upper gastrointestinal; DIC, disseminated intravascular coagulation; DM, diabetes mellitus; CHF, congestive heart failure; PE, pulmonary embolism; C5-C4, cervical vertebrae.

Three different NMBAs were used, including pancuronium in 19 subjects (61%), cisatracurium in 8 subjects (26%), and vecuronium in 4 subjects (13%). The median cumulative dose of each drug administered was pancuronium 300 mg (range 897 mg, interquartile range 327, M = 325, SD = 214), cisatracurium 1113 mg (range 4938 mg, interquartile range 3392, M = 1934, SD = 1829), and vecuronium 119 mg (range 233 mg, interquartile range 214, M = 127, SD = 103). The median duration of NMBA administration was 3 days (range 27 days, interquartile range 3.5, M = 5.55, SD = 6.5).

NMT returned promptly after NMBAs were discontinued in all subjects (median = 1 hour, M = 4.55, SD = 7.97). Muscle activity remained depressed by all measures. Muscle activity scores ranged from 0 to 5, with 10 of 31 subjects scoring 0 and only 3 subjects scoring 5 (Fig 1). Median recovery time for best scores was 12 hours (M = 12.96, SD = 9.67). Actigraphy counts were low at three intervals after NMBAs were discontinued: within 4 hours (median = 7.7 counts per minute, M = 18.25, SD = 36.7); 20 to 24 hours (median = 5.5, M = 13.25, SD = 28.6); and over the 24-hour period (median = 8.34, M = 9.09, SD = 4.73) (Fig 2). Although the median activity count was lower during the 20- to 24-hour period than in the first 4 hours after stopping NMBAs, a runs test of differences in median scores determined this was not statistically significant (P = .661). These values represent sharply depressed activity compared with actigraphy counts reported in the literature (35–80, M = 66). Thus, in satisfying the first aim of the study, these results indicate there was no relationship between recovery of NMT and functional muscle activity (Fig 3, Fig 4, Fig 5 and Fig 6).

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Fig 1. Dispersion of muscle activity scores within 24 hours after NMBAs. 0 = 32%; 1 = 10%; 2 = 13%; 3 = 29%; 4 = 3%; 5 = 10%. No movement or contraction = 0. Palpable contraction, no movement observed = 1. Movement at the joint with gravity eliminated = 2. Able to move the joint against gravity = 3. Able to move the joint against resistance, less than normal = 4. Fully normal strength = 5. NMBA, neuromuscular blocking agents.

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Fig 2. Comparison of actigraphy counts at three intervals after NMBAs. NMBA, neuromuscular blocking agents.

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Fig 3. Four-hour post-NMBA actigraphy counts and NMT. NMBA, neuromuscular blocking agents; NMT, neuromuscular transmission; TOF, train-of-four; HR, hours.

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Fig 4. Twenty- to 24-hour post-NMBA actigraphy counts and NMT recovery. NMBA, neuromuscular blocking agents; NMT, neuromuscular transmission; TOF, train-of-four; HR,.

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Fig 5. Average 24-hour post-NMBA actigraphy counts and NMT recovery. NMBA, neuromuscular blocking agents; NMT, neuromuscular transmission; TOF, train-of-four; HR,.

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Fig 6. Five-point muscle activity score recovery time and NMT recovery. NMBA, neuromuscular blocking agents; NMT, neuromuscular transmission; TOF, train-of-four; HR,.

The second aim of the study was to evaluate the relationship between delayed recovery of NMT or muscle activity and return of functional performance. Because only two subjects (5%) recovered functional performance within 24 hours, the results were not conducive to statistical analysis. However, an assessment of the relationship between short-term muscle weakness and long-term measures of recovery, time to extubation, and time to mobility (ambulation or chair transfer) was undertaken using chi-square analysis. Median time to extubation and initial mobility was 11 and 12.9 days, respectively. Actigraphy counts for the 2-day average was associated with time to extubation (χ2 = 5.98, df = 1, P = .014) and time to mobility (χ2 = 3.81, df = 1, P = .051). Also, muscle activity score recovery time was associated with time to mobility (χ2 = 5.07, df = 1, P = .024). These findings indicate that muscle weakness immediately after neuromuscular blockade influences functional performance (extubation and mobility) long after termination of NMBAs.

The third study aim was to identify predictors of delayed recovery and return of functional performance. Bivariate analyses identified several variables associated with depressed muscle activity. First, severity of illness was a factor, with APACHE score showing a relationship with actigraphy counts during the first 4 hours after NMBAs were stopped (n = 20, rs = −.556, P = .011). Second, altered renal function was associated with persistent muscle weakness. There was an inverse relationship between blood urea nitrogen (BUN) and actigraphy counts at 4 hours (n = 20, rs = −.732, P = .000) and creatinine 20 to 24 hours (n = 21, rs = −.462, P = .035) after terminating NMBAs, indicating that higher values in BUN and creatinine were associated with lower activity levels. Third, because a large number of subjects received propofol for a period of time during NMBA administration (mostly 1–2 days), a relationship between propofol use and muscle weakness was explored. There was an association between actigraphy counts and concurrent propofol use within 4 hours of terminating NMBAs (χ2 = 6.19, df = 2, P = .045), at the 20- to 24-hour interval (χ2 = 7.64, df = 2, P = .022) and the 2-day average actigraphy count (χ2 = 7.23, df = 2, P = .027). However, missing data spread unevenly across the actigraphy count categories and propofol use accounted for 2 degrees of freedom in the analysis and confounded the results. Furthermore, actigraphy counts for one of two subjects who received propofol during the first 4 hours after NMBAs were 165, the highest overall for all data-collection points; actigraphy data were missing for the second subject during this time frame. Actigraphy counts for the two subjects who received propofol during the 20- to 24-hour time period were 20.88, one of the two highest levels of activity during this interval, and .49.

After bivariate analyses, linear regression analysis was performed to determine the predictors of NMT and muscle activity recovery. Five separate analyses were performed with all indices of recovery except muscle score recovery time serving as dependent variables, including NMT recovery time, two determinations of actigraphy counts, time to mobility, and time to extubation. Too few subjects scored higher than 0 on the muscle score; thus, regression analysis was not plausible.

When NMT recovery time was entered into the analysis as the dependent variable, all independent variables were derived from the literature, because no associations were extrapolated from bivariate analyses of the other variables. Age, APACHE score, duration of NMBA infusion, cumulative dose of NMBA, BUN, and medications synergistic with NMBAs were entered stepwise into the model. Initial analysis of collinearity diagnostics showed BUN and creatinine were highly correlated, along with cumulative dose of NMBAs among the three agents. Therefore, only BUN was entered. Cumulative dose of pancuronium and vecuronium were collapsed and entered as one variable because they are both aminosteroid compounds with like dosing units, and cisatracurium was eliminated because only four subjects received the drug and the dosing unit differs from the other two drugs. A summary of the model indicated that no NMBA properties were associated with NMT recovery and that age was the only predictor variable (R2 = .509, F = 16.594, P = .001).

For the second analysis, actigraphy count at 4 hours after discontinuing NMBAs was entered into the regression model as the dependent variable, because bivariate analysis showed a relationship between APACHE score and BUN and actigraphy counts at the 4-hour interval. These variables, along with age, duration and cumulative dose of NMBA, synergistic drugs, and TOF recovery time were entered into the model as independent variables. The only predictor for muscle activity recovery at this interval was BUN (R2 = .313, F = 5.93, P = .030).

Actigraphy counts at the 20- to 24-hour endpoint were entered as the dependent variable for the next regression analysis. Both cumulative dose of NMBA and creatinine level were found on bivariate analysis to be associated with actigraphy counts at this interval and were entered into the model as independent variables along with age, APACHE score, duration of NMBA therapy, synergistic drugs, and TOF recovery time. Cumulative dose of NMBA was the only predictor variable (R2 = .311, F = 6.309, P = .025). In evaluating the long-term recovery variables time to extubation and time to mobility, data were available on relatively few subjects achieving extubation (n = 12) or mobility (n = 8). Thus, statistical analysis was not reportable.

In summary, there were two predictors of delayed muscle activity recovery, cumulative dose of aminosteroid NMBAs and impaired renal function, and one predictor of NMT recovery, age. There was no association between prolonged paralysis or weakness and steroid or aminoglycoside use, electrolyte or acid-base imbalance, or duration of NMBA therapy as reported in the literature.

Discussion

The study demonstrated severe depression in muscle activity during the first 24 hours after termination of neuromuscular blockade, which persisted for days to weeks in some cases, resulting in prolonged mechanical ventilation and delayed mobility. NMT returned promptly, which may provide further support for the hypothesis that there are two types of skeletal muscle weakness syndromes after neuromuscular blockade: “prolonged recovery” (short-term) and AQMS (long-term). It is possible, however, that there may be other explanations for the episodes of severe weakness observed in this study. For example, CIP and critical illness myopathy (CIM) are syndromes associated with severe weakness in critically ill patients. It has been hypothesized that a process of microcirculatory impairment induced by inflammatory mediators causes damage to motor neuron integrity.28 CIP and CIM are most frequently identified in patients with sepsis, acute organ dysfunction, and adult respiratory distress syndrome.28 Two subjects in the current study were diagnosed with sepsis, three with acute failure of one or two organs, and nine with ARDS. It is possible that many of these subjects developed CIP and/or CIM, which could explain severe weakness independent of NMBAs. However, without electrophysiology studies and muscle biopsies for confirmation, the presence of CIP or CIM is uncertain.

The benefits of peripheral nerve monitoring to guide medication titration and facilitate rapid recovery of NMT were clearly demonstrated. Appropriate dosing holds several advantages. First, direct costs of the drugs are reduced when dosing is carefully titrated to patient response and smaller quantities are given. Second, NMT must be restored before muscle movement is possible. Minimizing delay in resuming NMT allows initiation of muscle recovery and prevents complications of unnecessary immobility. Preventing complications is an important responsibility of nurses, which contributes to better overall patient outcomes and reduces costly iatrogenesis.

The results of five separate regression analyses determined that age, renal function, and cumulative dose of aminosteroid compounds were the best predictors of recovery of NMT and muscle activity after neuromuscular blockade. This underscores the importance of physiologic monitoring and assessment performed by critical care nurses, who must consider the factors associated with persistent weakness when caring for patients receiving NMBAs. Vigilant assessment and monitoring of physiologic function and response to NMBAs, with careful adjustments in dose, will contribute to improved recovery and avert complications of neuromuscular blockade. Because many medications, treatments, and patient conditions alter renal function, particularly in older patients, nurses play a critical role in preserving normal function and assessing for signs of renal compromise.

Knowledge of delayed muscle activity recovery is useful in determining the needs of patients who remain immobile, for example, measures to preserve pulmonary function, continued use of therapeutic beds to maintain skin integrity, medications and devices to prevent deep vein thrombosis, and analgesia and nonpharmacologic comfort measures.

Limitations

There were several limitations to the study. Missing data for measures of time to extubation and mobility because of a prolonged internal disaster at one of the facilities during data collection limited multiple analyses concerning these variables. Second, measurement of muscle strength by the 5-point scale is only useful in conscious, aware patients, and actigraphy has limited published use in critically ill patients. However, there was strong agreement between the two instruments in evaluating muscle weakness. Third, CNS-depressing effects of various sedatives and narcotics could have explained delays in recovery of muscle activity. The half-life of midazolam, lorazepam, haloperidol, and propofol ranges from 3 to 11, 8 to 15, 18 to 54, and 26 to 32 hours, respectively.11 However, no published reports were found describing delayed recovery after any of these medications that mimic the prolonged recovery effects of NMBAs. In contrast, benzodiazepines sometimes induce paradoxic agitation with excessive muscle activity, rather than severe weakness and inactivity.29 In addition, relative rapid awakening from propofol is reported, although slightly longer when infusions exceed 12 hours.30 Because only two subjects received propofol during the first 4 hours and two other subjects received propofol during the 20- to 24-hour period after termination of NMBAs, with two of those four time frames reflecting some of the higher actigraphy counts, propofol does not explain the overall delay in recovery of muscle activity. Controlled studies comparing muscle recovery times for patients receiving NMBAs and sedation versus sedation alone are needed.

Conclusion

Delays in time to recover muscle activity and extreme muscle weakness may occur despite prompt recovery of NMT. With ongoing advances in mechanical ventilation and other technology, especially with an aging population and comorbidity, predictably there will be a continued need for temporary, chemically induced paralysis and heavy sedation. Continued use of PNS and careful NMBA titration according to patient TOF response are warranted to minimize the cumulative dose and facilitate prompt recovery whenever possible. Clinicians should consider patient factors such as age and severity of illness when administering NMBAs and adjust the dose according to patient TOF response and goals of therapy. Targeted assessment of renal function during NMBA administration is recommended to anticipate dose reduction. Preventing prolonged effects of neuromuscular blockade that complicate recovery allows the individual to channel restorative processes toward recuperation from his or her underlying illness or injury. This facilitates earlier resumption of normal activities and roles, contributing to quality of life for persons with critical illness and injury. Averting the cascade of events associated with prolonged immobility helps to reduce length of stay, decrease consumption of resources, and shrink the astronomic costs of care associated with prolonged immobility. Continued investigation of problems relative to recovery from neuromuscular blockade is indicated. Prospective, randomized, controlled trials are needed to evaluate benefits and muscle recovery for NMBAs and sedatives versus sedatives alone, because of the potentially confounding effects of sedatives and hypnotics on muscle activity in the current study.

References

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[FormerEMSLT297]

Heah KEVKEI,, the naemsp web site link did not come up and I couldn't find it,, summarize for us,, are they for it or against it.

RSI involves a lot more than just knocking someone out and putting in an E.T. tube. The first thing you need to do is look at a patients airway and determine the class of airway based on the Mallampati class 1-4....

the size of the tongue vs size of pharynx,, the ability of the patient to extend their atlanto-occipital joint,, simply put the ability of the patient to flex and extend thier neck, size of teeth or other dental issues... presence or absence of tonsils,,,,,etc..

If the patient has NO NECK and is like 5'5 300 Lbs. they are probably not a good candidate for RSI...

That being said,,, RSI is a great tool in the pre-hospital care arsenal if used properly and performed by skilled clinicians.

My agency sends all of its paramedics to a Minimum 40 hours in an O.R. with an Anesthesiologist to learn to utilize the medications, perform the skills and do a good pre hospital airway exam.

All RSI's performed go through a mandatory QA/QI review by the Medical Director and follow up is done at the hospital to determine long term patient outcome.... My opinion about RSI is that in some cases where a patient needs an airway and they are not being oxygenated witha BVM and O2,, then RSI is one way of definitavely securing an airway.

[paramedicmike]

The first thing you need to do is look at a patients airway and determine the class of airway based on the Mallampati class 1-4....

How do you assess a mallampati score on a patient who really needs RSI? Do you ask them to sit up and stick their tongue out? What about that immobilized patient? There are other ways of assessing an airway and determining the potential for a difficult airway. Assessing a mallampati score shouldn't be the *first* thing you do. Nor will it be feasible in just about every RSI scenario out there.

Check the EMS Book Club thread in "EMS Discussions". There's an excellent airway manual listed there that should help you.

[Ace844]

For all of you who are interested in learning more about this I'd like to direct you to this thread here:: Teaching Points:::: Intubation-RSI In addition to doing a further search on 'the city' as well.

Hope This Helps,

ACE844

[FormerEMSLT297]

... right,,, i mis spoke,, or mis typed as it were,,, the first thing you need to do is determine if the patient is a candidate,, and that involves MANY MANY factors,,, v/s signs sx of hypoxia, hypo ventilation,,, etc,... then if you think based on v/s the patient is a candidate, assess anatomical factors that may make RSI difficult,, like no chin ,,, lack of thyromental distance less than 6cm, large teeth, etc..

It can be difficult even impossible to assess the Mallampati scale in trauma patients.... but other factors like ease of ventilation with a BVM,, V/S including pulse ox.... need to be checked before you go about paralyzing someone and actually stopping their ability to breath... just so that you can "get a tube" or do a skill like someone else suggested...

RSI is serious business, and a decision to perform it should not be entered into lightly without a through assessment and a high probability of success.

[ffmedic9588]

How do you assess a mallampati score on a patient who really needs RSI? Do you ask them to sit up and stick their tongue out? What about that immobilized patient? There are other ways of assessing an airway and determining the potential for a difficult airway. Assessing a mallampati score shouldn't be the *first* thing you do. Nor will it be feasible in just about every RSI scenario out there.

You can also assess a difficult airway with LEMON. I believe that most practioners can determine a difficult airway by just looking externally at the patient.

[paramedicmike]

That's what I was getting at. Chances are you're not going to get a mallampati score on any patient requiring emergent airway management.

That's also why I mentioned the Ron Wall book on airway management in the City Book Group thread. It goes into great detail on airway assessments including the "LEMON" acronym as well as others.

-be safe.

[AZCEP]

Using the LEMON for the unconscious and the 3-3-2 rule for the semi-responsive makes life much easier, but why would we want to do that?:wink:

Take every chance to assess an airway. Just like every other assessment you do, practice makes it a much more natural process. When the time comes that you need to decide how to secure an airway, it will be second nature for you.

[Ace844]

Using the LEMON for the unconscious and the 3-3-2 rule for the semi-responsive makes life much easier, but why would we want to do that?:wink:

Take every chance to assess an airway. Just like every other assessment you do, practice makes it a much more natural process. When the time comes that you need to decide how to secure an airway, it will be second nature for you.

THAT SOUNDS TOO MUCH LIKE COMMON SENSE...WE CAN'T DO THAT!!!