During November 18, 2014, and May 5, 2015, 50 patients were consecutively screened for eligibility, 40 of whom (20 LOCM, 20 IOCM) were included in the study (15 females, 25 males; mean age 61.79 years; range, 30–79 years). Eight patients were excluded by the exclusion criteria and 2 patients because the procedure could not be performed. All patients completed the study, and there were no follow-up losses (Figure 1). There were no CM-related adverse events. The baseline characteristics of participants in both CM groups were comparable (Table 2).
Arterial Blood Pressure
After administration of CM and NSS, systemic blood pressures showed a typical hemodynamic temporal course. Compared to the initial value obtained 1 minute before administration, systemic blood pressure first showed a slight increase, followed by a variable decrease and after 3 minutes recovery to initial and compensatory levels higher than initial (Figures 2 and 3). We did not alter the infusion or administer additional vasopressors so as to not skew the data.
Mean time from commencement of CM administration to decline in blood pressure was 65 ± 36 seconds for LOCM and 73 ± 43 seconds for IOCM. Time from onset of decline in blood pressure to normotension was 105 ± 61 seconds (range, 25–300 seconds) for LOCM and 112 ± 20 seconds (range, 90–145 seconds) for IOCM. A decrease in systolic blood pressures exceeding 25 mm Hg with systemic hypotension (systolic pressure <80 mm Hg) was observed only after LOCM administration (Table 3 and Figure 2). The mean systolic/diastolic pressure values after CM administration decreased to 79/43 mm Hg for LOCM and 119/62 mm Hg for IOCM (P < .001). Twelve (60%) of the 20 patients in the LOCM group had systolic pressure <80 mm Hg and mean arterial pressure <55 mm Hg, with the lowest mean arterial pressure being 39 mm Hg. Compared to baseline values obtained 1 minute before CM administration, LOCM resulted in a mean systolic/diastolic decrease of 31/16 mm Hg. Statistically significant differences in systolic and diastolic blood pressure values were found for time (systolic pressure P < .001, diastolic pressure P < .001), time × group interaction (systolic pressure P < .001, diastolic pressure P < .001), and group comparison (systolic pressure P = .002, diastolic pressure P = .012).
No statistically significant differences in systemic blood pressure were observed between the first and the second CM administration for either LOCM or IOCM.
Administration of NSS demonstrated a slight initial rise in systemic blood pressure similar to that for CM (P > .640; Figure 3). Comparing the lowest values following LOCM and NSS administration, statistically significant differences in systolic (28 ± 17 mm Hg; P < .001), diastolic (12 ± 6 mm Hg; P < .001), and mean arterial pressure (18 ± 9 mm Hg; P < .001) were detected. Three minutes after administration, systemic pressures were seen to have increased significantly more for LOCM, with differences of 9 ± 16 (P = .013), 4 ± 7 (P = .013), and 6 ± 11 mm Hg (P = .024), respectively.
Heart rate measured when systemic blood pressure was at its lowest showed 62.9 ± 11.7 bpm in the LOCM versus 55.7 ± 10.3 bpm in the IOCM group (P =.042). Compared to baseline values 1 minute before CM application, LOCM resulted in a median (interquartile range) increase in heart rate of 4 (2–11) bpm and IOCM of 1 (1.5–3.5) bpm (P = .043).
Under inspiratory oxygen flow of 0.35 to 0.45 fraction of inspired oxygen (FIO2) peripheral saturation showed differences of 1% ± 2%, as measured when systemic blood pressure was at its lowest. There were no statistically significant differences between LOCM and IOCM with regard to oxygen saturation.
Per-Hour Urine Output
Urine output was higher after administration of LOCM as compared to IOCM (P = .006). Median per-hour urine output (interquartile range) related to body weight was 3.7 (1.7–4.4) mL/h/kg in the LOCM group and 1.8 (0.7–2.3) mL/h in the IOCM group (P = .010). Forty-eight hours after treatment, no significant differences were seen in serum creatinine concentration (P = .541).
The main findings of this study highlight the self-limited decrease in arterial blood pressure following administration of LOCM. Compared with the baseline value obtained 1 minute before administration, LOCM resulted in a mean systolic/diastolic decrease of 31/16 mm Hg.
Average heart rate and rise in heart rate were more pronounced following LOCM administration, presumably due to a compensatory reaction to hypotension. Svensson et al14 published an average heart rate and heart rate variation of 64.0 and 4.4 bpm after LOCM and 59.6 and 1.4 bpm after IOCM, which are well comparable with our results.
Intraoperative hypotension defined as any episode of systolic blood pressure <80 mm Hg or at least 1 episode of systolic blood pressure >20% below baseline was observed in 60% of our patients.15
Clinical relevance of these findings may arise from the fact that anesthesiologists working in the radiology department have to be aware of potential side effects of CM with regard to intolerance, organ function, and perfusion that might necessitate postoperative observation. In addition, anesthetists and radiologists should be aware of these effects in patients in whom episodes of disturbed tissue microcirculation may pose a clinical risk. In particular, elderly patients with a medical history of severe cardiac disease and renal dysfunction have an increased risk for mortality due to adverse CM reactions.16 , 17
Duration of intraoperative intervals of hypotension directly correlates with adverse cardiac- and renal-related outcomes.9 Even 1 to 5 minutes of intraoperative mean arterial pressure <55 mm Hg can be clinically relevant with adjusted odds ratios of 1.18 for acute kidney injury, 1.30 for myocardial injury, 1.35 for cardiac complication, and 1.16 for 30-day mortality.9 In our study, mean blood pressure <55 mm Hg was observed in 12 of the 20 patients following LOCM administration, with the lowest mean pressure of 39 mm Hg and the interval between decrease and return to baseline blood pressure lasting up to 300 seconds (105 ± 61 seconds).
Bach et al18 observed a significant reduction in blood flow velocity in downstream capillaries as early as 10 seconds after administration of iopromide 370. The maximum effect was seen 30 seconds after administration, and it subsided within 120 seconds. This observation corresponds with our clinical findings, but cannot be explained solely by viscosity of the given CM. LOCM decreases tissue oxygen tension, and myocardial partial pressure of oxygen in the left coronary artery declines significantly after administration of iopromide 370.5 Changes in erythrocyte morphology, for example, echinocyte formation, can contribute to diminished capillary blood flow.19 Furthermore, buckling of venous endothelial cells within 90 seconds of exposure to iopromide 370 can significantly diminish venous blood flow.20 We hypothesize that the self-limited significant drops in arterial blood pressure observed in our study are caused by temporary morphologic and functional changes in blood and endothelial cells immediately after LOCM administration. However, additional interactions via nitrous oxide, prostacyclins, or endothelin-1 have to be taken into account.21
In a recent meta-analysis, 3 studies showed a strong association between in-hospital cardiovascular events and administration of LOCM.22 In cardiac high-risk patients with a history of acute myocardial infarction, unstable angina, and/or myocardial ischemia following myocardial infarction, Davidson et al23 reported 45% fewer major adverse cardiac events when using IOCM during percutaneous transluminal coronary angioplasty. Arrhythmia was more frequently observed.14 In animal studies, drop in myocardial oxygen partial pressure and recovery intervals were observed to last considerably longer following LOCM than following IOCM.5 , 24 Wysowski and Nourjah17 observed that most deaths attributed to x-ray CM were associated with renal failure or nephropathy, anaphylaxis, and allergic reactions. Ten percent were related to cardiopulmonary arrest, 8% to respiratory failure, and 4% to stroke and cerebral hypoxia.17 The hemodynamic effects of CM may play a contributing role in adverse reactions and complications.17
In our study, LOCM showed a significant diuresis with a 2-fold higher per-hour urine output than IOCM. We attribute this finding to the physiologic osmotic diuretic effect of low-osmolar contrast media. Serum creatinine 48 hours after the intervention was unaffected by the use of either CM.
The number of patients was rather small, but the differences in the analyzed end points were highly significant. We cannot tell whether results from iopromide administration differ from other LOCMs.
The repeated measures design of our study stipulated CM-enhanced CT scan twice, before planning of the ablation and for final verification of ablation size in each patient. NSS was administered during nonenhanced CT scan for verification of proper needle placement. This sequence of treatments allowed investigations without alterations of the SRFA treatment procedure. Hypothetically speaking, the washout period between treatments could have induced a carryover effect and impairment of kidney function caused by the first CM administration could have altered the volume effects of NSS with regard to duration and intensity. However, we did not observe significant differences between the first and the second application of CM and between NSS in both groups.
Hypotensive effects of anesthesia can prolong the circulation time and increase duration of exposure to CM. We cannot exclude that differences between dosing of sevoflurane and propofol might have affected the hemodynamic profile of patients.
In our study, effects of general anesthesia on blood pressure were counteracted with very low-dosed continuous norepinephrine infusion right from the beginning in all patients. We cannot exclude that increased peripheral vascular resistance by norepinephrine might have altered the hemodynamic changes following contrast.
The results were obtained in patients under general anesthesia who were normotensive and may not be extrapolated to the clinical condition of nonanesthetized humans who are hypotensive. Furthermore, the study population was composed of patients with liver disease. We cannot tell whether CM-related hemodynamic effects differ from those in patients without liver disease.
This is the first randomized controlled prospective evaluation of hemodynamic effects following intravenous administration of LOCM and IOCM in patients under general anesthesia. LOCM produced a self-limited systemic hypotension and rise in heart rate that was statistically significantly different from that of IOCM. In light of the increasing number of radiologic interventions performed under general anesthesia, anesthetists and radiologists should be aware of these effects during CM-enhanced CT scans, especially in selected patients in whom short episodes of hypotension may pose a high clinical risk.
We thank the radiation technologists of the RFA laboratory and the anesthetic nurses and technologists of the Department of Anesthesiology and Critical Care Medicine for their conscientious assistance.
Name: Gerlig Widmann, MD.
Contribution: This author was the principal investigator and helped conceive and design the work, interpret the data for the work, draft the work, and finally approve the work.
Name: Reto Bale, MD.
Contribution: This author was the co-investigator and helped design the work, interpret the data in the work, critically revised the work, and finally approve the version.
Name: Hanno Ulmer, PhD.
Contribution: This author was the co-investigator and helped statistically design the work, statistically analyze the data in the work, critically revise the work, and finally approve the version.
Name: Daniel Putzer, MD.
Contribution: This author was the co-investigator and helped acquire the data in the work, critically revise the work, and finally approve the version.
Name: Peter Schullian, MD.
Contribution: This author was the co-investigator and helped acquire the data in the work, critically revise the work, and finally approve the version.
Name: Franz-Josef Wiedermann, MD.
Contribution: This author was the co-investigator and helped conceive the work, critically revise the work, and finally approve the version.
Name: Wolfgang Lederer, MD.
Contribution: This author was the co-investigator and helped conceive and design the work, interpret the data for the work, draft and revise the work, and finally approve the work.
This manuscript was handled by: Roman M. Sniecinski, MD.
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© 2018 International Anesthesia Research Society
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