Paralytics for Rapid Sequence Intubation

Rapid sequence intubation (RSI) is a process whereby an induction agent and a neuromuscular blocking agent are given in rapid succession to facilitate endotracheal intubation

The selection of a specific sedative depends on multiple factors: the clinical scenario, which includes patient factors (includes cardiorespiratory and neurologic status, allergies, comorbidity) and the clinician's experience/training and institutional factors, as well as the characteristics of the paralytic

Succinylcholine remains the most commonly used paralyzing agent, however, it does have pharmacologic considerations

The use of rocuronium continues to increase due to its unique pharmacologic profile and its niche is becoming prevalent in situations where the risk of hyperkalemia and bradycardia are high

Patanwala, 2011 | Retrospective analysis/ n=327 | Succinylcholine 1.65 mg/kg vs Rocuronium 1.19 mg/kg | The rate of first-attempt intubation success was similar between the succinylcholine and rocuronium groups (72.6% vs. 72.9%, p = 0.95).

Watt, 2012 | retrospective cohort study/ n=200 | Succinylcholine 1.7 +/- 0.7 mg/kg vs Rocuronium 1.3 +/- 0.4 mg/kg | After intubation, 77.5% (n=155) of patients were initiated on a sedative infusion of propofol (n=148) or midazolam (n=7). Mean time to post intubation sedation was significantly greater with rocuronium compared to succinylcholine (27 min vs 15; p <0.001)

Smith 2002 | Prospective, blinded Study/ n=100 | Rocuronium 1 mg/kg vs Vecuronium 0.15 mg/kg | Intubation was successful in 95% of patients in the vecuronium group and 100% in the rocuronium group

Weiss,1997 | RCT/ n=45 | Succinylcholine 1.5 mg/kg vs Rocuronium 0.7 and 0.9mg/kg | Rocuronium bromide at a dose of 0.9 mg/kg provides intubating conditions similar to succinylcholine 1.5 mg/kg at 1 minute. Intubating conditions at 1 minute following rocuronium 0.7 mg/kg inferior to higher dose of rocuronium or succinylcholine.

Magorian 1993 | RCT/ n= 50 | Succinylcholine 1 mg/kg vs Rocuronium 0.6, 0.9, and 1.2 mg/kg vs Vecuronium 0.1 mg/kg | Onset time of rocuronium 0.9 mg/kg and 1.2 mg/kg rocuronium and succinylcholine 1 mg/kg) were similar; onset times fo rocuronium 0.6 mg/kg and vecuronium mg/kg) were much longer. Rocuronium (1.2 mg/kg) had a mean onset time of 55 seconds, which was similar to the mean onset time of succinylcholine (50 seconds)

Author, year | Design/ sample size | Intervention & Comparison | Outcome

April, 2018 | Prospective cohort study/ n= 4,275 | Succinylcholine >= 1.5 mg/kg vs Rocuronium >= 1.2 mg/kg | First-pass intubation success rate was no difference between the agents with 87.0% with succinylcholine versus 87.5% with rocuronium (adjusted OR 0.9; 95% CI 0.6- 1.3 Incidence of any adverse events were no difference There was a difference in first pass intubation success with rocuronium >= 1.2 mg/kg compared to (<1.2 mg/kg)

Tran, 2017 | Cochrane Meta-Analysis/ n= 4151 | Succinylcholine >= 1 mg/kg vs Rocuronium >= 0.6 mg/kg | Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions (risk ratio (95%CI) 0.86 (0.81 to 0.92), n = 4151) and clinically acceptable intubation conditions (risk ratio (95%CI) 0.97 (0.95-0.99), n = 3992). A high incidence of detection bias amongst the trials

Patanwala, 2016 | Retrospective cohort study/ n=233 | Succinylcholine (dosing not reported) vs Rocuronium (dosing not reported) | In the high-severity TBI patients, succinylcholine was associated with increased mortality compared with rocuronium (OR 4.10, 95% CI 1.18-14.12).

Patanwala, 2011 | Retrospective analysis/ n=327 | Succinylcholine 1.65 mg/kg vs Rocuronium 1.19 mg/kg | The rate of first-attempt intubation success was similar between the succinylcholine and rocuronium groups (72.6% vs. 72.9%, p = 0.95).

Watt, 2012 | retrospective cohort study/ n=200 | Succinylcholine 1.7 +/- 0.7 mg/kg vs Rocuronium 1.3 +/- 0.4 mg/kg | After intubation, 77.5% (n=155) of patients were initiated on a sedative infusion of propofol (n=148) or midazolam (n=7). Mean time to post intubation sedation was significantly greater with rocuronium compared to succinylcholine (27 min vs 15; p <0.001)

Smith 2002 | Prospective, blinded Study/ n=100 | Rocuronium 1 mg/kg vs Vecuronium 0.15 mg/kg | Intubation was successful in 95% of patients in the vecuronium group and 100% in the rocuronium group

Weiss,1997 | RCT/ n=45 | Succinylcholine 1.5 mg/kg vs Rocuronium 0.7 and 0.9mg/kg | Rocuronium bromide at a dose of 0.9 mg/kg provides intubating conditions similar to succinylcholine 1.5 mg/kg at 1 minute. Intubating conditions at 1 minute following rocuronium 0.7 mg/kg inferior to higher dose of rocuronium or succinylcholine.

Magorian 1993 | RCT/ n= 50 | Succinylcholine 1 mg/kg vs Rocuronium 0.6, 0.9, and 1.2 mg/kg vs Vecuronium 0.1 mg/kg | Onset time of rocuronium 0.9 mg/kg and 1.2 mg/kg rocuronium and succinylcholine 1 mg/kg) were similar; onset times fo rocuronium 0.6 mg/kg and vecuronium mg/kg) were much longer. Rocuronium (1.2 mg/kg) had a mean onset time of 55 seconds, which was similar to the mean onset time of succinylcholine (50 seconds)

Succinylcholine | Shorter duration of paralysis | Can see hyper-K with CNS/spinal cord injury (>3 days), myopathies, burns (few days late), IA sepsis, critical illness, and occasionally with severe traumatic injury acutely due to succinic acid mechanism. Avoid sux when possible in pediatric populations (<8)

Rocuronium | Has reversal agent, not associated with malignant hyperthermia, not associated with hyperkalemia (no fasciculation), dosed on ideal body weight (100mg will give 1.2 mg/kg for male that is 6'4) Certain centers (not GHS) may have access to sugammadex (Bridion) instead of neostigmine + atropine for reversal. | Longer paralytic time, however has reversal agent

Overview of Evidence | Overview of Evidence | Overview of Evidence | Overview of Evidence

Author, year | Design/ sample size | Intervention & Comparison | Outcome

April, 2018 | Prospective cohort study/ n= 4,275 | Succinylcholine >= 1.5 mg/kg vs Rocuronium >= 1.2 mg/kg | First-pass intubation success rate was no difference between the agents with 87.0% with succinylcholine versus 87.5% with rocuronium (adjusted OR 0.9; 95% CI 0.6- 1.3 Incidence of any adverse events were no difference There was a difference in first pass intubation success with rocuronium >= 1.2 mg/kg compared to (<1.2 mg/kg)

Tran, 2017 | Cochrane Meta-Analysis/ n= 4151 | Succinylcholine >= 1 mg/kg vs Rocuronium >= 0.6 mg/kg | Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions (risk ratio (95%CI) 0.86 (0.81 to 0.92), n = 4151) and clinically acceptable intubation conditions (risk ratio (95%CI) 0.97 (0.95-0.99), n = 3992). A high incidence of detection bias amongst the trials

Patanwala, 2016 | Retrospective cohort study/ n=233 | Succinylcholine (dosing not reported) vs Rocuronium (dosing not reported) | In the high-severity TBI patients, succinylcholine was associated with increased mortality compared with rocuronium (OR 4.10, 95% CI 1.18-14.12).

Patanwala, 2011 | Retrospective analysis/ n=327 | Succinylcholine 1.65 mg/kg vs Rocuronium 1.19 mg/kg | The rate of first-attempt intubation success was similar between the succinylcholine and rocuronium groups (72.6% vs. 72.9%, p = 0.95).

Watt, 2012 | retrospective cohort study/ n=200 | Succinylcholine 1.7 +/- 0.7 mg/kg vs Rocuronium 1.3 +/- 0.4 mg/kg | After intubation, 77.5% (n=155) of patients were initiated on a sedative infusion of propofol (n=148) or midazolam (n=7). Mean time to post intubation sedation was significantly greater with rocuronium compared to succinylcholine (27 min vs 15; p <0.001)

Smith 2002 | Prospective, blinded Study/ n=100 | Rocuronium 1 mg/kg vs Vecuronium 0.15 mg/kg | Intubation was successful in 95% of patients in the vecuronium group and 100% in the rocuronium group

Weiss,1997 | RCT/ n=45 | Succinylcholine 1.5 mg/kg vs Rocuronium 0.7 and 0.9mg/kg | Rocuronium bromide at a dose of 0.9 mg/kg provides intubating conditions similar to succinylcholine 1.5 mg/kg at 1 minute. Intubating conditions at 1 minute following rocuronium 0.7 mg/kg inferior to higher dose of rocuronium or succinylcholine.

Magorian 1993 | RCT/ n= 50 | Succinylcholine 1 mg/kg vs Rocuronium 0.6, 0.9, and 1.2 mg/kg vs Vecuronium 0.1 mg/kg | Onset time of rocuronium 0.9 mg/kg and 1.2 mg/kg rocuronium and succinylcholine 1 mg/kg) were similar; onset times fo rocuronium 0.6 mg/kg and vecuronium mg/kg) were much longer. Rocuronium (1.2 mg/kg) had a mean onset time of 55 seconds, which was similar to the mean onset time of succinylcholine (50 seconds)

Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from http://www.micromedexsolutions.com/

Magorian. Anesthesiology. 1993;79:913-918.

Smith CE. Air Med J. 2002;21:26-32.

Weiss JH. J Clin Anesth. 1997 Aug;9(5):379-82.

Patanwala S. Acad Emerg Med. 2011 Jan;18(1):10-4.

Patanwala S. Pharmacotherapy. 2016 Jan;36(1):57-63.

Tran DTT. Anaesthesia. 2017 Jun;72(6):765-777

April MD. Ann Emerg Med. 2018 Dec;72(6):645-653.

Succinylcholine | Rocuronium

Dose | IV: 1.5 mg/kg; IM: 3-4 mg/kg (ABW) | 1-1.2 mg/kg (IBW)

Administration | IV push | IV Push

Formulation | 200 mg/ 10 ml vial (must be refrigerated) | 100 mg/10 ml vial (non-refrigerated)

PK/PD | Onset: 40-60 seconds Duration: 4-10 minutes Metabolism: Rapidly hydrolyzed by plasma pseudocholinesterase to inactive metabolites Renal Excretion:10% | Onset: ~ IV 45-90 seconds Duration: 30-90 minutes Metabolism: N- demethylation Renal Excretion:

Adverse Effects | Bradycardia, Hyperkalemia, fasciculations, ↑ intraocular pressure, transient ↑ ICP ~5-10 mmHg, malignant hyperthermia (rare) | Very few reported Increased peripheral vascular resistance (abdominal aortic surgery)

Drug Interactions | No major reactions | No major reactions

Compatibility | Incompatible with sodium bicarbonate, nafcillin, oxacillin, phenytoin, phenobarbital | Incompatible with furosemide, regular insulin, lorazepam, phenytoin, pantoprazole, and Zosyn

Succinylcholine | Rocuronium

Contraindications | Hypersensitivity to succinylcholine or any component of the formulation; personal or familial history of malignant hyperthermia; skeletal muscle myopathies; >3-5 days following major burns, intra-abdominal sepsis, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury. | Hypersensitivity to rocuronium

Advantages per EM Physicians | Considerations per EM Physicians

Succinylcholine | Shorter duration of paralysis | Can see hyper-K with CNS/spinal cord injury (>3 days), myopathies, burns (few days late), IA sepsis, critical illness, and occasionally with severe traumatic injury acutely due to succinic acid mechanism. Avoid sux when possible in pediatric populations (<8)

Rocuronium | Has reversal agent, not associated with malignant hyperthermia, not associated with hyperkalemia (no fasciculation), dosed on ideal body weight (100mg will give 1.2 mg/kg for male that is 6'4) Certain centers (not GHS) may have access to sugammadex (Bridion) instead of neostigmine + atropine for reversal. | Longer paralytic time, however has reversal agent

Overview of Evidence | Overview of Evidence | Overview of Evidence | Overview of Evidence

Author, year | Design/ sample size | Intervention & Comparison | Outcome

April, 2018 | Prospective cohort study/ n= 4,275 | Succinylcholine >= 1.5 mg/kg vs Rocuronium >= 1.2 mg/kg | First-pass intubation success rate was no difference between the agents with 87.0% with succinylcholine versus 87.5% with rocuronium (adjusted OR 0.9; 95% CI 0.6- 1.3 Incidence of any adverse events were no difference There was a difference in first pass intubation success with rocuronium >= 1.2 mg/kg compared to (<1.2 mg/kg)

Tran, 2017 | Cochrane Meta-Analysis/ n= 4151 | Succinylcholine >= 1 mg/kg vs Rocuronium >= 0.6 mg/kg | Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions (risk ratio (95%CI) 0.86 (0.81 to 0.92), n = 4151) and clinically acceptable intubation conditions (risk ratio (95%CI) 0.97 (0.95-0.99), n = 3992). A high incidence of detection bias amongst the trials

Patanwala, 2016 | Retrospective cohort study/ n=233 | Succinylcholine (dosing not reported) vs Rocuronium (dosing not reported) | In the high-severity TBI patients, succinylcholine was associated with increased mortality compared with rocuronium (OR 4.10, 95% CI 1.18-14.12).

Patanwala, 2011 | Retrospective analysis/ n=327 | Succinylcholine 1.65 mg/kg vs Rocuronium 1.19 mg/kg | The rate of first-attempt intubation success was similar between the succinylcholine and rocuronium groups (72.6% vs. 72.9%, p = 0.95).

Watt, 2012 | retrospective cohort study/ n=200 | Succinylcholine 1.7 +/- 0.7 mg/kg vs Rocuronium 1.3 +/- 0.4 mg/kg | After intubation, 77.5% (n=155) of patients were initiated on a sedative infusion of propofol (n=148) or midazolam (n=7). Mean time to post intubation sedation was significantly greater with rocuronium compared to succinylcholine (27 min vs 15; p <0.001)

Smith 2002 | Prospective, blinded Study/ n=100 | Rocuronium 1 mg/kg vs Vecuronium 0.15 mg/kg | Intubation was successful in 95% of patients in the vecuronium group and 100% in the rocuronium group

Weiss,1997 | RCT/ n=45 | Succinylcholine 1.5 mg/kg vs Rocuronium 0.7 and 0.9mg/kg | Rocuronium bromide at a dose of 0.9 mg/kg provides intubating conditions similar to succinylcholine 1.5 mg/kg at 1 minute. Intubating conditions at 1 minute following rocuronium 0.7 mg/kg inferior to higher dose of rocuronium or succinylcholine.

Magorian 1993 | RCT/ n= 50 | Succinylcholine 1 mg/kg vs Rocuronium 0.6, 0.9, and 1.2 mg/kg vs Vecuronium 0.1 mg/kg | Onset time of rocuronium 0.9 mg/kg and 1.2 mg/kg rocuronium and succinylcholine 1 mg/kg) were similar; onset times fo rocuronium 0.6 mg/kg and vecuronium mg/kg) were much longer. Rocuronium (1.2 mg/kg) had a mean onset time of 55 seconds, which was similar to the mean onset time of succinylcholine (50 seconds)