Patients
This prospective, observational study was conducted between 26/07/2016 and 30/10/2018 in the 1st Department of Surgery, Semmelweis University, Budapest, Hungary. Ethics approval for this study was provided by Semmelweis University Regional and Institutional Committee of Science and Research Ethics, Budapest, Hungary (Registration number: 144/2016, date of approval: 25/07/2016). Informed consent was obtained from each subject. Patients aged ≥18 years who were scheduled for elective general surgery under general anesthesia on predetermined weekdays were included if they met the eligibility criteria and all necessary data were available. The inclusion and exclusion criteria are shown in Table 1. As a conceptual summary, we included elective, premedicated patients and excluded those who were already hypotensive or severely hypertensive, those considered to be at high risk or those having a clinical condition that would prevent the adequate evaluation of either the IVC (e.g., significant tricuspid regurgitation) or blood pressure changes (e.g., pheochromocytoma).
Table 1
Inclusion criteria
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Exclusion criteria
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Age ≥18 years
Elective surgery
General anesthesia
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ASA physical status > 3
Dyspnea
Systolic blood pressure ≥180 mmHg
Systolic blood pressure <90 mmHg
Decompensated heart failure
Elevated pulmonary arterial pressure >40 mmHg
Significant valvular disease
Significant carotid stenosis
Documented negative fluid balance >1.000 ml on preceding day
Pheochromocytoma
SOFA score > 1
Agitation (RASS > 1)
IVC non visualized
Epidural catheter in use
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ASA American Society of Anesthesiology, IVC inferior vena cava, RASS Richmond Agitation Sedation Scale, SOFA Sepsis-related Organ Failure Assessment
Study design
Eligible patients were screened using ultrasonography. The inferior vena cava was identified, and characteristics were recorded in the dorsal recumbent position under light sedation (RASS 0- -1) and spontaneous breathing. The collapsibility index (IVCCI) was calculated, and two groups were formed according to the measured IVCCI: the collapsing group characterized by IVCCI≥50% (CI+) and the noncollapsing group (CI-) (in whom the IVCCI was<50%). This level was arbitrarily set with regard to the results in previously published literature, verifying that IVCCI values between 40% and 50% measured in spontaneously breathing patients are predictive for volume responsiveness in different clinical settings [14] [15] [16].
Vital signs were recorded, and protocolled anesthesia induction was performed. Two minutes after drug administration but before intubating the trachea, the vital signs were measured again. The hemodynamic response was characterized in each group with the change in systolic blood pressure as the end point. Anesthesia-related hypotensive events were recorded if the systolic blood pressure dropped below 90 mmHg or a ≥30% drop in initial systolic pressure was observed.
Ultrasonographic measurements
Patients in the surgical ward were evaluated before transportation to the operating room. Ultrasonographic scans were performed by one of four adequately trained independent anesthesiologists who had undergone institutional training for ultrasound use in anesthesia and who had at least two years of experience in the field. One of two ultrasound machines was used (Sonosite Titan - FUJIFILM SonoSite, Inc. Bothell, Washington, United States and Hitachi Aloka Noblus, Hitachi Healthcare, Tokyo, Japan). Both machines were equipped with a curvilinear transducer (5 MHz). The inferior vena cava was visualized in B-mode from a longitudinal paramedian subxyphoid view; when a good echographic window was not available, an intercostal, transhepatic lateral view was used. The last section of the vein, which was proximal to the hepatic vein inflow and 0.5-3 cm from the right atrium, was selected for the M-mode, and measurements were performed as recommended in the consensus document of the American and European Cardiologic Societies [17]. The maximal expiratory diameter of the vein was recorded (dIVC expiration) under normal breathing of the lightly sedated patient, and the collapsibility index (IVCCI) was calculated using the following formula: (dIVC expiration – dIVC inspiration) / dIVC expiration × 100 = IVCCI. The IVC diameter at expiration and inspiration had to be measured during the same respiratory cycle. Figure 1 represents a typical highly collapsing IVC.
Anesthesiologic practice
Routine premedication using alprazolam was given one hour before surgery. Regular cardiovascular medication of the patients was maintained on their established routine, except for diuretics and angiotensin-converting inhibitors, which were withdrawn. All patients were monitored continuously using ECG, pulse oximetry and capnography starting from the beginning of manual ventilation. Noninvasive blood pressure monitoring by oscillometry and invasive arterial blood pressure monitoring were used at the discretion of the anesthesiologist according to the details of the planned surgery and the risk level of the patient. Noninvasive measurements were obtained at 5 minute intervals, and an additional measurement was obligatory 2 minutes after induction drug administration. This step preceded the intubation of the trachea. If invasive monitoring was used, an arterial cannula was inserted before induction, and postinduction vital signs were registered at the same time points as above. To induce general anesthesia, our institutional standard practice of using fentanyl (1-2 μg/kg), propofol (1,5-2 mg/kg) and nondepolarizing muscle relaxants (rocuronium or cis-atracurium) according to age, weight, chronic organ function and the needs of the surgery was not changed for study purposes.
Statistical analysis
Sample size
To calculate the sample size, the change in systolic blood pressure after induction drug administration was the variable of interest. A minimum difference of 15 mmHg was considered clinically important, and that in combination with a standard deviation of 25 mmHg coming from our pilot data of 103 patients not involved in the study were used for the calculations. A type one error of 0.05 and a required power of 0.80 were set. Assuming unequal study groups with a 1 to 3 ratio of patients having collapsing (CI+) and noncollapsing (CI-) IVC, we used corrected sample sizes [18]. A minimum of 81 patients were required based on the conditions detailed above. To maintain adequate power in cases of a lack of adherence to the protocol or methodological failure, an additional 25 percent was screened, and a total of 102 patients were enrolled.
Data analysis
Data were pooled for analysis in Microsoft Excel 2013 (Additional file 1); for the statistical analysis, we used StatsDirect Statistical Software (Version 3.1.20, Stats Direct Ltd, Grantchester, Cambridge, UK). Continuous variables are presented as the means±standard deviation if they were normally distributed as tested by the Shapiro-Wilk W test. Nonnormally distributed data are shown as the medians and interquartile ranges. Student’s two-sample t-test and the Mann-Whitney U test were used for comparisons. Categorical variables are shown as percentages and absolute numbers of cases. The χ2 and Fisher exact test were used for contingency table analysis as appropriate. Two-sided p-values are shown, and the limit of statistical significance was set to p<0.05.
The 50% value of IVCCI as a diagnostic cutoff value was evaluated by calculating the sensitivity, specificity, and positive and negative predictive values. Previously cited literature [14] data highlight the potential cutoff level for IVCCI of 40%; this value was also tested. The receiver operating characteristics curve was plotted, and the area under the curve was calculated by Wilcoxon’s method, and the standard error was calculated according to the method by DeLong. In these calculations, a composite definition of hypotension was used. Postinduction systolic pressure less than 90 mmHg and/or a more than 30 percent decrease from the baseline systolic pressure was needed to treat data as positive for hypotension.