Patients
This prospective, observational study was conducted between 26/07/2016 to 30/10/2018 in the Ist Department of Surgery, Semmelweis University, Budapest, Hungary. Ethical 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 required from each subject. Patients age≥18 years scheduled for elective abdominal surgery under general anesthesia on predetermined weekdays were included if eligibility criteria were met, investigational necessities were available. Inclusion and exclusion criteria are shown in Table 1. As a conceptual summary, we involved elective, premedicated patients excluding actually hypotensive or severely hypertensive subjects, ones considered to be in any of some high risk states or those having a clinical condition which disables adequate evaluation of either IVC (e.g. significant tricuspid regurgitation) or blood pressure changes (e.g. pheochromocytoma).
Study design
Eligible patients were screened using ultrasonography. Inferior vena cava was identified and characteristics were recorded in dorsal recumbent position under light sedation (RASS 0- -1) and spontaneous breathing. Collapsibility index (IVCCI) was calculated and two groups were formed according to the measured IVCCI: Collapsing group characterized by IVCCI≥50% (CI+) and non-collapsing group (CI-) (where IVCCI<50%). This level was arbitrarily set with a regard to literature results verifying IVCCI values between 40% and 50% measured on spontaneously breathing patients are predictable for volume responsiveness in different clinical settings [12] [13] [14].
Vital parameters were recorded and a protocolled anesthesia induction was performed. Two minutes after drug administration, but before intubating the trachea, vital signs were repeatedly measured. Hemodynamic response was characterized in each group with change in systolic blood pressure as an end point. Anesthesia related hypotensive event was recorded if systolic blood pressure dropped below 90 mmHg or ≥30% drop of initial systolic pressure was observed.
Ultrasonographic measurements
Patients at the operating block were evaluated before transportation to the operating room. Ultrasonographic scans were performed by one of four adequately trained independent anesthesiologists having accomplished an institutional training for ultrasound use in anesthesia and having at least two years experience in the field. One of the 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). Inferior vena cava was visualized in B-mode from a longitudinal paramedian subxyphoid view or when a good echographic window was not available, an intercostal, transhepatic lateral view was used. The last section of the vein, proximal to the hepatic vein inflow, 0.5-3 cm from the right atrium was selected for M-mode and measurements were performed as recommended in the consensus document of American and European Cardiologic Societies [15]. Maximal expiratory diameter of the vein was recorded (dIVC expiration), under normal breathing of the light sedated patient and collapsibility index (IVCCI) was calculated using the formula: (dIVC expiration – dIVC inspiration) / dIVC expiration × 100 = IVCCI. IVC diameter at expiration and inspiration had to be measured during the same respiratory cycle. Figure 1 represents a typical collapsing IVC.
Anesthesiological practice
Routine premedication using alprazolam was given one hour before surgery. Regular cardiovascular medication of the patients was maintained on their regular basis, except for diuretics and angiotensin converting inhibitors, which were withdrawn. All patients were monitored continuously using ECG, pulseoxymetry and additionally by capnography started from the beginning of manual ventilation. Noninvasive blood pressure monitoring by oscillometry and invasive arterial blood pressure monitoring were used by the discretion of the anaesthesiologist according to the necessities of the planned surgery and the patients’ risk. Noninvasive measurements were set to repeated measurements at 5 minutes 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, arterial cannula was inserted before induction and postinductional vital signs were registered at the same time points as above. For inducing general anaesthesia our institutional standard practice of using fentanyl (1-2 μg/kg), propofol (1,5-2 mg/kg) and non-depolarizing muscle relaxants (rocuronium or cis-atracurium) according to age, weight, chronic organ function and needs of surgery was not changed for study purposes.
Statistical analysis
Sample size
For calculating sample size, the change in systolic blood pressure after inductional drug administration was the variable of interest. A minimal difference of 15 mmHg considered clinically important and a standard deviation of 25 mmHg coming from our audit data of 103 patients not involved in the study were used for calculations. Type one error of 0.05 and a required power of 0.80 were set. Assuming unequal study groups with 1 to 3 ratio of patients having collapsing (CI+) and non-collapsing (CI-) IVC we used corrected sample sizes [16]. A minimum of 81 patients were required with the conditions detailed above. For keeping adequate power in case of protocol violence 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, for statistical methods we used StatsDirect Statistical Software (Version 3.1.20, Stats Direct Ltd, Grantchester, Cambridge, UK). Continuous variables are presented as mean±standard deviation if they were normally distributed tested by Shapiro-Wilk W test, non-normally distributed data are shown as median and interquartile range. Student’s two sample t-test and Mann Whitney U test were used for comparison respectively. Categorical variables are shown as percentages and absolute number of cases. χ2 and Fisher’s exact test were used for contingency table analysis where appropriate. Two sided p-values are shown, limit of statistical significance was set to p < 0.05.
50% value of IVCCI as a diagnostic test was evaluated by calculating sensitivity, specificity, positive and negative predictive values. Receiver operating characteristics curve was plotted and area under curve was calculated by Wilcoxon’s method and standard error according to DeLong. In these calculations a composite definition of hypotension was used. Postinductional systolic pressure less than 90 mmHg and/or a more than 30 percent decrease from baseline systolic pressure was needed to treat data as positive for hypotension.