1. Sensitivity Analyses
Intraoperative neuromuscular blocking agent administration and hospital readmission
Sub-cohort
Frequency of readmitted patients
(percent of quintile in sub-cohort)
Odds Ratio
for 5th vs. 1st NMBA
ED95 dose quintile
[95% CI],
p values
P for trend,
p value
1st NMBA ED95 dose quintile
5th NMBA ED95 dose quintile
ASA physical status score
<3
(n=9361)
53 (2.5%)
171 (11.0%)
1.55 [ ],
p=0.049
z=11.3,
p<0.001 ≥3
(n=3761)
41 (8.3%)
161 (15.2%)
1.53
[ ],
p=0.07
z=3.73,
Duration of surgery
<120 minutes
(n=6266)
70 (3.0%)
12 (11.1%)
2.15
[ ],
p=0.04
z=5.9,
≥120 minutes
(n=6856)
24 (8.8%)
320 (12.8%)
1.98
[ ],
p=0.02
z=4.57,
Charlson Comorbidity Index
(n=9251)
50 (2.3%)
134 (9.9%)
1.81
[ ],
p=0.01
z=10.17,
(n=3871)
44 (10.7%)
198 (15.7%)
1.27 [ ],
p=0.29
z=2.51,
Including patients who died in hospital (n=13226)
94 (3.6%)
332 (12.7%)
1.53 [ ],
z=11.15,
Liver resection (n=485)
6 (6.2%)
14 (14.4%)
10.69
[ ], p=0.13
z=3.84,
Gastrectomy (n=151)
3 (9.7%)
7 (23.3%)
1.53 [ ],
p=0.42
z=5.49,
Colorectal resection (n=176)
8 (22.2%)
11 (31.4%)
1.31 [ ],
p=0.22
z=1.25,
Laparoscopic cholecystectomy (n=3309)
8 (1.2%)
34 (5.1%)
2.92 [ ],
p=0.03
z=3.98,
Hernia repair (n=1670)
4 (1.2%)
20 (6.0%)
2.73 [ ],
p=0.11
z=3.49,
Inpatient surgical procedures (n= 9952)
75 (6.9%)
565 (11.3 %)
1.22
[ ], p=0.24
z=5.73,
p<0.01
Ambulatory surgical procedures (n=3167)
19 (9.6%)
9 (1.6%)
2.61
[ ], p=0.03
z=4.25
Tharusan Thevathasan cand med1, Shirley Shih MD2 , Kyan C. Safavi MD1, David L. Berger MD3, Sara M. Burns MS1, Anne M. Que MS1,
Stephanie D. Grabitz cand med1, Ross D. Zafonte, DO2,
Matthias Eikermann MD PhD1, Jeffrey C. Schneider MD2
Massachusetts General Hospital, Harvard Medical School and Spaulding Rehabilitation Hospital:
1 Department of Anesthesia, Critical Care and Pain Medicine
2 Department of Physical Medicine and Rehabilitation Service
3 Department of Surgery
Study PI and Correspondence: Dr. Matthias Eikermann MD PhD,
Introduction
Results
High prevalence of hospital readmissions continues to be a challenge for the healthcare system, with implications for the quality of patient care and excess financial costs (> $52 billion in the USA in 2013). CMS now publicly report 30-day readmission data and have implemented financial penalties towards hospitals with excess 30-day readmissions. (1-4)
Anesthesiologists use different strategies to optimize surgical relaxation: neuraxial anesthesia, inhalational anesthetics, opioids, neuromuscular blocking agents (NMBA). NMBA dose is associated with an increased risk of postoperative respiratory complications. (5)
Hypothesis: Intraoperative NMBA dose is associated with 30-day readmission to the hospital.
Study subject flow diagram
Primary and secondary outcomes
P for trend: z=64.02, p<0.001
P for trend: z=13.03, p<0.001
P for trend: z=70.08, p<0.001
Methods
Characteristics of study population
Study population
Consecutively enrolled cohort of adult patients who underwent abdominal surgery under general anesthesia at MGH between 01/2007 and 08/2014
Exposure
Quintiles of intraoperatively administered NMBA ED95 dose
Primary outcome
30-day hospital readmission
Secondary outcomes
Hospital length of stay, hospital costs
Subgroup analyses
Variations in surgical duration, ASA physical status, Charlson comorbidity status, and abdominal surgical subtypes on 30-day hospital readmission
Exploratory analyses
Effect modification of 30-day hospital readmission by admission type (ambulatory vs. inpatient surgery), major respiratory complications and by inclusion of patients who died in the hospital
Statistical method
A priori defined multivariable logistic and negative binomial regression models adjusted for 22 confounders accounting for underlying and acute patient characteristics and demographics, procedural complexity and duration as well as NMBA pharmaco-kinetics (benzylisoquinoline vs. steroid-type; low vs. high potency), intraoperative respiratory and hemodynamic parameters and administered drugs (such as opioids, vasopressors or NMBA reversal agents).
NMBA dose quintile
1st
2nd
3rd
4th
5th
Total
Multiples of NMBA ED95 dose equivalent
(median, IQR) 0*
(0-1.18)
1.83
( )
2.56
( )
3.47
( )
5.58
( )
( )
Age (years)
(Median, IQR)
51 (38-63)
50 (36-62)
53 (40-65)
55 (42-66)
57 (45-67)
Male (per cent)
1178 (44.9)
1141 (43.4)
1191 (45.4)
1163 (44.3)
1276 (48.8)
5949
BMI (Mean, SD)
29.95 (7.27)
29.90 (7.62)
29.47 (8.11)
29.64 (9.03)
27.73 (7.89)
29.34 (8.05)
Charlson Comorbidity Index (Median, IQR)
0 (0-2)
1 (0-3)
2 (0-4)
2 (1-8)
ASA physical status (Mean, SD)
2.06 (0.59)
2.04 (0.64)
2.20 (0.63)
2.27 (0.62)
2.38 (0.58)
2.19 (0.63)
Emergency case (per cent)
234 (8.9)
308 (11.7)
252 (9.6)
178 (6.8)
116 (4.4)
1088
Duration of surgery (min) (Mean, SD)
73 (38)
105 (45)
136 (63)
176 (74)
278 (120)
153 (102)
Procedural rcomplexity (Median, IQR)
27.6
( )
31.76
( )
33.34
( )
46.46
( )
57.23
( )
35.2
( )
Work RVU
10.47
( )
10.47 ( )
14.46
( )
20.89
( )
29.4
( )
15.38
( )
Neuraxial anaesthesia
(per cent)
79 (3.0)
210 (8.0)
439 (16.7)
730 (27.8)
1206 (46.1)
2664
Neostigmine dose (mg) (Mean, SD)
1.44 (1.83)
3.21 (1.51)
3.33 (1.57)
3.38 (1.58)
3.39 (1.63)
2.95 (1.79)
NMBA dose quintile
1st
2nd
3rd
4th
5th
Total
Vasopressor dose (norepinephrine equivalent; mcg min-1) (Mean, SD)
0.05 (0.41)
0.08 (0.20)
0.14 (0.35)
0.21 (0.40)
0.50 (0.84)
0.19 (0.52)
Morphine equivalent (without fentanyl; mg) (Mean, SD)
0.19 (1.11)
0.38 (1.62)
0.58 (2.15)
0.91 (2.91)
0.82 (2.96)
0.58 (2.28)
Fentanyl (mcg) (Mean, SD)
(93.14)
(87.68)
(91.66)
(94.08)
(112.22)
(99.75)
FiO2 (Mean, SD)
59.05 (17.40)
58.0
(15.05)
57.53 (14.60)
57.62 (13.66)
58.84 (15.34)
58.21 (15.27)
Fluid resuscitation (ml) (Mean, SD)
(531.90)
(869.94)
(973.27)
(1864.3)
( )
( )
Hypotensive minutes
(Mean, SD)
0.66 (1.60)
0.98 (2.58)
1.27 (6.06)
1.60 (4.45)
3.17 (7.43)
1.54 (4.99)
Protective ventilation
(per cent)16
1046 (39.8)
1154 (43.9)
1284 (48.9)
1278 (48.6)
1369 (52.4)
6131
Ambulatory same-day surgical procedures
(per cent)
1534 (58.4)
923 (35.1)
483 (18.4%)
207 (7.9%)
20 (0.8%)
3167
Inpatient surgical procedure
1090 (41.6)
1708 (64.9)
2143 (81.6)
2420 (92.1)
2594 (99.2)
9955
NMBA dose histograms
Conclusion
References
Dose-dependent relationship between intraoperative NMBA dose and increased risk of 30-day hospital readmission after abdominal surgery, an effect that is modified in patients undergoing ambulatory surgical procedures
This study is the first to test the association between intraoperative neuromuscular blocking agent administration and the risk of 30-day hospital readmission in patients undergoing abdominal surgery.
(1) American Hospital Association. TrendWatch 2011.
(2) Barrett et al. Agency for Healthcare Research and Quality (US) 2015.
(3) Fingar et al. Agency for Healthcare Research and Quality (US) 2015.
(4) Centers for Medicare & Medicaid Services. Readmissions Reduction Program (HRRP).
(5) Eikermann et al. Anesthesiology 2015