SUPPLEMENT CONTENT
Supplement 1 – Search strategy
Key word conceptsConcept MeSH Keyword
Rocuronium 1‐(17‐(acetoyl)‐3‐hydroxy‐2‐(4‐morpholinyl)androstan‐
16‐yl)‐1‐(2‐propenyl)pyrrolidinium
Rocuronium
rocuronium bromide Zemuron
pyrrolidinium, 1‐((2beta,3alpha,5alpha,16beta,17beta)‐
17‐(acetyloxy)‐3‐hydroxy‐2‐(4‐morpholinyl)androstan‐
16‐yl)‐1‐(2‐propenyl)‐, bromide
Esmeron
Esmeron Esmerone
Esmerone ORG‐9426
ORG‐9426 ORG 9426
ORG 9426 Zemuron
Infusions pump Perfusion Pumps Infus*
Perfusion Pump Perfus*
Pump, Perfusion Drug Delivery Systems
Pumps, Perfusion Pump
Infusors Infusor
Pumps, Infusion Infusion Pump Pump, Infusion
Intravenous Drug Delivery Systems Drug Infusion Systems
Drug Infusion System Infusion System, Drug Infusion Systems, Drug System, Drug Infusion Systems, Drug Infusion Infusion Pumps, External External Infusion Pump External Infusion Pumps Infusion Pump, External Pump, External Infusion Pumps, External Infusion
Deep or intense NMB
Deep and intense NMB is characterized by the monitoring of post‐tetanic count stimuli (1‐2 and 0 respectively).
deep intense profound post‐tetanic PTC tetanic count
Search syntax Search engine (28‐06‐2018)
Syntax
Rocuronium infusion for deep or intense NMB (Rocuronium OR Zemuron OR Esmeron OR Esmerone OR ORG‐9426 OR ORG 9426) AND (Infus* OR Perfus* OR Drug
Delivery Systems OR Pump) AND (deep OR intense OR profound OR post‐tetanic OR PTC OR tetanic count OR
posttetanic OR post tetanic) PubMed
(all fields)
43 Web of science
(All databases)
33 Cochrane Library
(title, abstract, keywords)
63
Other searches 94
TOTAL 233
Supplement 2 – Inclusion and exclusion criteria
Inclusion criteria1) Human adults (over 18 years old) classified as ASA I‐IV;
2) Randomized clinical trials, controlled trials and cohort studies;
3) Included studies that conduct surgical procedure with general anesthesia with rocuronium through continuous infusion as muscle relaxation anesthesia for profound neuromuscular blockade (PTC of 0‐2);
4) Reported data on amount of rocuronium administered during the procedure, rating of surgical conditions or reversal time after 4mg.kg‐1 of Sugammadex;
5) Includes comparative outcomes of moderate NMB or intermittent rocuronium administration.
Exclusion criteria
1) Studies including pediatric or animal as participants;
2) Case reports studies;
3) Moderate NMB level as target objective;
4) Bolus only as the administration method to maintain profound NMB;
5) Use of other NMBA to maintain profound NMB.
NMB ‐ Neuromuscular blockade; NMBA – Neuromuscular blockade agents; PTC – Post‐tetanic count.
Supplement 3 ‐ Excluded studies
Author Year Motif
Boon M. 2013 Study protocol
Kim H. S. 2009 Not profound NMB target Kopman A. F. 2005 Not profound NMB target Liu Y. 2017 Not profound NMB target Lee J. H. 2016 Case‐report
Van Brantegem E. 2014 Insufficient data reported
Yamamoto S. 2015 Unfit comparative group assignment Rex C. 2009 Unfit comparative group assignment Smetana K. S. 2017 Review
Soto‐Mesa D. 2015 Not profound NMB target Veelo D. P. 2015 protocol
Lee H. J. 2015 Unfit comparative group assignment Nonaka T. 2013 Unfit comparative group assignment Georgiev S. 2011 Not profound NMB target
Makri I. 2011 Review
Supplement 4 ‐ Included studies characteristics
A. Participants and surgery profileAUTHOR (year) Sample size Age (y) BMI (kg/m‐1) ASA Surgical procedure
Baete S. (2017) 30/30 41/42 40/41 I‐III Laparoscopic surgery
Yoo Y. C. (2015) 34/32 63.9/61.5 23.6/24.4 I‐II Laparoscopic surgery
Madsen M. V. (2017) 65/63 63/65 26/25 I‐III Upper laparotomy
Kim M. H. (2016) 30/31 57.1/56.8 23.0/24.2 I‐III Laparoscopic surgery Martini C. H. (2014) 12/12 53.5/55* 25.9/25.8 I‐III Laparoscopic surgery Staehr‐Rye A. K. (2014) 25/23 45.25/47.5* 26.75/26.25* I‐II Laparoscopic surgery Kim H. J. (2019) 28/28 57/50.25* 24/23* I‐III Robotic gastrectomy
Mekawy N. (2012) 40/0 N/A/‐ 29.8/‐ I‐II Endoscopic sinus surgery
B. Intervention and outcome characteristics
AUTHOR (year)
REASEARCH TYPE
INTERVENTION
COMPARISON
OUTCOME
Rocuronium administration Monitoring Sugammadex reversal
Induction dose (mg/kg)
Initial infusion
rate (mg.kg‐1.h‐1) Adjustments Device Nerve CAL PTC target
Stimuli interval (min)
Time point Amount
(mg/kg) Primary Secondary and other
Baete S.
(2017)
Randomized trial
0.6 0.6 Target titrated
TOF Watch SX
Ulnar yes 1‐2 5 End of
surgery 4 Moderate vs.
Deep NMB
SRS; IAP;
duration of surgery
Postoperative pulmonary function; need for postoperative respiratory support; Administered rocuronium (mg.kg‐1), remifentanil and propofol;
time from TOFR >0.9 to pulmonary function tests Yoo Y. C.
(2015) 1 0.6 Target titrated Fascial yes 1‐2 15 End of
surgery N/A Moderate vs.
Deep NMB IOP
SRS; IAP; Administered rocuronium (mg);
postoperative pain; postoperative respiratory events;
Madsen M. V.
(2017) 0.6 N/A Add bolus Ulnar yes 0‐1 3‐5 End of
anesthesia 4‐16
Moderate vs.
Deep NMB;
bolus vs.
infusion
SRS
Surgical rating score at instances, need for intervention; operating time, wound dehiscence or infections; adverse events
Kim M. H.
(2016) 0.6 N/A Target titrated Ulnar N/A
1‐2 N/A End of
surgery 2‐4 Moderate vs.
Deep NMB IAP
Surgical conditions (5‐stage satisfaction scale);
perioperative respiratory and cardiovascular parameters; postoperative recovery profiles; pain and nausea intensity; Administered rocuronium (mg);
Martini C. H.
(2014) 1 0.6
Add bolus + adjust infusion
rate
Ulnar yes 1‐2 15 End of
surgery 4 Moderate vs.
Deep NMB SRS
Level of agreement between anesthetists and surgeon on surgical conditions; effects on hemodynamic variables; time to TOF.0.9 (min);
relevant variables in the PACU; Administered rocuronium (mg)
Staehr‐Rye A. K.
(2014) 0.3+0.7 0.3‐0.4 Target titrated Ulnar yes 0‐1 3‐4 End of
surgery 2‐8 Moderate vs.
Deep NMB
Surgical conditions
Time of surgery, proportion of procedures completed with IAP of 8 mm Hg; pain;
postoperative consumption of analgesics;
antiemetics; incidence and time of postoperative events; Administered rocuronium (mg);
Kim H. J.
(2019) 1 0.3
Add bolus + adjust infusion
rate
Ulnar yes 1‐2 10 End of
surgery 4 Moderate vs.
Deep NMB
Quality of recovery
postoperative day 1
Quality of recovery postoperative day 2;
intraoperative hemodynamics and respiratory data; Postoperative pain, nausea, vomiting, and medication use; administered rocuronium (mg);
Mekawy N.
(2012) 0.6 0.6‐0.9 Target titrated TOF guard Ulnar yes 1‐2 N/A T2 4
Conventional vs.
Sugammadex reversal
Recovery profile
Postoperative Respiratory System Evaluation Score; Administered rocuronium (mg); Reversal recovery time (min)
Abbreviations: NMB ‐ Neuromuscular blockade; PTC – Post‐tetanic count; CAL – Monitor device calibration; SRS – Surgical Rating Scale; NRS – numeric rating scale (0‐100) IAP – Internal Abdominal
Supplement 5 ‐ Risk of bias and quality assessment
AUTHOR Random sequence generation Allocation concealment Blinding of participants and personnel Blinding of outcome assessment Incomplete outcome data Selective reporting Other bias
Baete S. Low Low Low Low Low Low Low
Yoo Y. C. Low Low Low Low Low Low Low
Madsen M. V. Low Low Unclear Low Low Low High
Kim M. H. Low Low Low Low Low Low High
Martini C. H. Low Unclear Low Low Low Low Low
Staehr‐Rye A. K. Low Low High Low Low Low Low
Kim H. J. Low Low Low Low Low Low Low
Mekawy N. Low Unclear Unclear High Low Low Unclear
High Unclear Low
Supplement 6 – Surgical conditions sensitive analysis A. Studies with the lowest risk of other bias are included
B. Studies with target PTC 1‐2 are included
