This study was approved by the ethics committee of West China Hospital (approval number: 2017 − 434) and registered with the Chinese Clinical Trial Registry (registration number: chiCTR2100046109). This study was performed in accordance with the Declaration of Helsinki, patients who underwent elective otorhinolaryngology surgery at West China Hospital under general anaesthesia with endotracheal intubation between March and August 2017 were included in the study (Table 1).
Table 1
Demographic and clinical characteristics of patients undergoing IV induction
variable
|
All patients
|
NP(n = 53)
|
GAIH(n = 70)
|
p
|
Age(year)
|
|
|
0.106
|
≤ 65
|
50(94.4)
|
61(85.9)
|
|
༞65
|
3(5.7)
|
10(14.1)
|
|
Gender
|
|
|
0.800
|
Male
|
23 (43.4)
|
33 (46.5)
|
|
Female
|
30 (56.6)
|
38 (53.5)
|
|
ASA
|
|
|
0.103
|
I ~ II
|
45(84.9)
|
66 (94.3)
|
|
III ~ IV
|
8(15.1)
|
4 (5.7)
|
|
BMI(kg/m2)
|
|
|
0.647
|
BMI ≤ 24
|
42 (79.2)
|
53 (75.7)
|
|
BMI༞24
|
11 (20.8)
|
17 (24.3)
|
|
Hypertension
|
6(11.3)
|
11 (15.7)
|
0.488
|
diabetes
|
2(3.8)
|
4 (5.7)
|
0.624
|
CHD
|
1(1.9)
|
1 (1.4)
|
0.844
|
Smoking
|
5(9.4)
|
7 (10.0)
|
0.917
|
Drinking
|
4(7.5)
|
4 (5.7)
|
0.686
|
Baseline MAP
|
85.17(12.67)
|
85.89(17.14)
|
0.790
|
PreECG
|
|
|
0.068
|
Normal
|
50(94.3)
|
59 (84.3)
|
|
Premature
|
|
2 (2.9)
|
|
Bradycardia
|
1(1.9)
|
1 (1.4)
|
|
Tachycardia
|
|
2 (2.9)
|
|
ST-T change
|
1(1.9)
|
5 (7.1)
|
|
Dpropofol (mg/kg)
|
2.20(0.72)
|
2.15 (0.65)
|
0.575
|
Dsufentanil (ug/kg)
|
0.30(0.12)
|
0.24 (0.15)
|
0.041*
|
Dmidazolam (mg/kg)
|
0.037(0.10)
|
0.034 (0.0078)
|
0.224
|
Tpropofol
|
-4.13 (1.78)
|
-3.27 (1.69)
|
0.007*
|
Tsufentanil
|
-4.64 (1.68)
|
-3.84 (1.44)
|
0.005*
|
Tmidazolam
|
-5.12(1.71)
|
-4.62(1.12)
|
0.089
|
Ppropofol
|
-2.51 (1.86)
|
-1.61 (1.68)
|
0.006*
|
Psufentanil
|
0.37 (1.66)
|
0.43 (1.68)
|
0.823
|
Pmidazolam
|
-2.44(1.68)
|
-1.55(1.40)
|
0.006*
|
Maintain
|
|
|
༜0.001*
|
No
|
9 (17.0)
|
31 (44.3)
|
|
Inhalational
|
19 (35.8)
|
22 (31.4)
|
|
Intravenous
|
10 (18.9)
|
10 (14.3)
|
|
Inhalational + Intravenous
|
15 (28.3)
|
7 (10.0)
|
|
CHD: chronic heart disease; Dsufentanil: dose of sufentanil; Dmidazolam: dose of midazolam; Tpropofol: administration time of propofol; Tsufentanil: administration time of sufentanyl; Tmidazolam: administration time of midazolam; Ppropofol: peak effect time of propofol; Psufentanil: peak effect time of sufentanil; Pmidazolam: peak effect time of midazolam |
* denotes statistical significance compared with NP group (P\(<\)0.05) |
Nineteen individuals were excluded from our trial because of inhalational induction, large dosage opioid-benzodiazepine induction, local nerve blockade anaesthesia before induction, or unsuccessful intubation or difficult airway (Fig. 1). In compliance with the privacy policy, patient anaesthetic records were recorded using the Patient Data Management and Review system (mindray corporation, USA).
The primary endpoint in our investigation was the development of GAIH, which was defined as a drop in MAP of more than 30% from baseline [2], whereas a change in MAP of less than 30% was classified as normal blood pressure (NP). The baseline data for MAP were collected from the time the patient entered the operating room until induction began, and records were only included in our study if the MAP was monitored every 1 minute.
Demographical, dose-related, and time-related risk factors for GAIH were categorised. ASA classification, age, gender, BMI, and medical history were all used as demographic factors. In our investigation, anaesthesia was inducted using propofol, sufentanil, midazolam, cisatrocurum, or rocuronium, and dose-related predictors were standardized to body weight and divided into groups according to clinical dose range.
The peak effect time of administering drugs was used to define time-related predictors. To describe the time points (Fig. 2), we defined the start of induction as the first administration of induction drug and the end of induction as 15 minutes after the last intravenous injection (or the end of recording with the onset of surgery), dividing the induction into intervals 1 and 2 by intubation. Furthermore, we set the time of intubation to “0” minute, so the agents used before or after intubation were recorded as Tanesthetics with positive or negative values (e.g. Tanesthetics=-2 min means a drug was given 2 minutes before intubation, and this period belongs to interval 1), and Panesthetics was calculated based on the peak effect time of Tanesthetics (e.g. Tpropofol=-2 min, Ppropofol=Tpropofol+1.6 min=-0.4 min, means if propofol was given 2 min before intubation, the peak effect of propofol was suggested to reach 0.4 min before intubation)[9].
2.1. Sample size calculation and statistical analysis
NCSS PASS version 11.0 (NCSS LLC, Kaysville, Utah, USA) was used to compute sample size, which was based on a target number of 10 outcome occurrences per independent variable [10]. SPSS software version 23.0 was used for statistical analysis (IBM Corp., Armonk, NY, USA). Logistic regression modeling was used to analyze the effect of variables on the risk factors for GAIH.
Based on a two-tailed significance threshold of 0.05 (estimated 70–90% incidence of GAIH)[10], at least 92 patients [4] were estimated to discern the difference with 90% power. A multiple logistic regression model with 6 or less predictor variables was thus allowed.
Before logistic regression, continuous variates were categorized according to the least hemodynamic changes[11–14]. Continuous data were first reported as mean (SD) or median (interquartile range), as appropriate, and the difference between groups were analyzed using the Manne-Whitney U test. The categorical data were presented as proportion percentages and were analyzed using the \({\chi }2\) test or Fisher’s exact test. Variables with p < 0.05 in the univariate analysis were subsequently allocated in a multivariate binary logistic regression mode testing. Multicollinearity were assessed between independent risk factors by using variance inflation factors (VIF) with a reference value of 10. Risk factors was confirmed by the backward LR method in both univariate and multivariate logistic regression. Results of logistic regression analysis was presented as odds ratio (OR) with 95% confidence intervals (CI), the level of significance was P\(<\)0.05.