This article is accompanied by the following Invited Commentary:
Saugel B, Scheeren TWL. Continuous non-invasive haemodynamic monitoring: a beneficial impact on patient outcome is needed to gain ‘confidence in the technology’. Eur J Anaesthesiol 2017; 34:713–715.
Hypotension during general anaesthesia is a risk factor for the development of acute kidney injury,1 stroke2 or myocardial infarction.3,4 Many drugs used for induction and maintenance of anaesthesia have a negative inotropic effect,5,6 which may cause hypotension. Patients suffering from chronic arterial hypertension are at increased risk of hypotension and of developing complications associated with this due to altered lower limits of blood flow auto-regulation.4
To detect and treat intraoperative hypotension, a patient's blood pressure (BP) is monitored during general anaesthesia. A variety of monitoring techniques are available. In most cases, BP is monitored intermittently by means of the oscillometric method by using an upper arm cuff.7 This technique is non-invasive and readily available for use. However, due to the intermittent measurement, changes in BP are not detected immediately. Although continuous intra-arterial BP monitoring is the gold standard, the insertion of a catheter into an artery can lead to complications such as bleeding, embolism or blood stream infection8 and hence, before use, the advantages and disadvantages need careful consideration. A third way of monitoring BP is now available by using continuous non-invasive technologies such as the volume clamp method or radial artery applanation tonometry.9–11 Real-time monitoring of BP without the insertion of an arterial catheter is possible with devices utilising one of these measurement principles.
Given the availability of either intermittent or continuous BP measuring technologies, it is of interest whether continuous BP monitoring has an impact on a patient's BP stability during general anaesthesia.
We therefore designed our study to investigate the effect of continuous monitoring (volume clamp technique) on BP stability during induction and maintenance of general anaesthesia in orthopaedic patients.
Materials and methods
The purpose of the study was to observe if, under clinical conditions, the presence of continuous BP measurement makes any difference in terms of the occurrence of hypotension or hypertension, or in the requirements for norepinephrine or fluid administration in patients undergoing general anaesthesia. The investigation was designed as a randomised controlled study with a 1 : 1 allocation ratio.
The study was approved on 10 June 2015 under the protocol number 290-15 by the local ethics committee (Ethikkommission bei der LMU München, Chairman W. Eisenmerger) and registered at ClinicalTrials.gov (registration number NCT02519101). It was conducted at a German university hospital from June 2015 to May 2016.
Patients eligible for inclusion in the study were those requiring orthopaedic surgery under general anaesthesia of at least 2 h duration, with an American Society of Anesthesiologists physical status classification of II or III and with a history of arterial hypertension, already diagnosed and being treated by the general practitioner. Patients who required frequent arterial blood samples or for whom admission to the ICU after surgery was planned were excluded. All patients gave written informed consent before study inclusion.
After inclusion, patients were randomised either to the control group or the study group. Allocation was performed by using sealed opaque envelopes. Screening, inclusion and randomisation were performed by investigators who were not involved in the care of the patients (ASM and JSN). Before anaesthesia, the required BP monitoring was set up by a nurse. In both groups, oscillometric measurements (Dräger Infinity; Lübeck, Germany) were recorded at 3-min intervals throughout the procedure (this is the local clinical standard for frequency of intraoperative BP monitoring). In addition, patients in the study group received continuous non-invasive measurement by using the ClearSight device (Edwards, Irvine, California, USA), which displays an arterial pressure waveform based on the volume clamp method.12 The continuous non-invasive arterial BP and its waveform were displayed both on the stand-alone ClearSight monitor and on the main anaesthesia monitor, alongside other vital parameters. Whenever possible, the continuous measurement device and the upper arm cuff were placed on the patient on opposite arms. All clinical decisions were made by the attending anaesthetists, including individualised doses of anaesthetic and vasopressor drugs. Importantly, to minimise the possibility of the attending anaesthetists acting differently from their normal routine (e.g. paying special attention to BP changes or treating hypotension more aggressively than usual), they were not made aware of the purpose of the study. As allocation to groups could not be concealed, anaesthetists were informed that the purpose of the study was to compare BP measurements between the two techniques, and that a control group was necessary to ensure that the BP values in the study group were representative.
General anaesthesia was induced by injection of sufentanil and propofol. The baseline BP was obtained simultaneously with the injection of sufentanil at the beginning of the anaesthesia. Rocuronium was given to facilitate endotracheal intubation. Maintenance of anaesthesia was either by continuous infusion of propofol or by inhalation of sevoflurane/air/oxygen, combined with bolus doses of sufentanil or a continuous infusion of remifentanil. In some cases, an epidural catheter was inserted before induction of anaesthesia, and was used intraoperatively and for postoperative pain management. The different types of anaesthetic were not controlled between the groups. If hypotension occurred (i.e. a mean arterial pressure <60 mmHg), norepinephrine was given. Norepinephrine was the first-choice vasopressor, given either as a continuous infusion or as a bolus. Hypertension was defined as mean BP more than 140 mmHg.
Every hour after induction of anaesthesia, the cumulative norepinephrine dosage, the amount of fluid administered and the urine output (if a urinary catheter was present) were documented in a case report form. Both intermittent and continuous BP data were recorded automatically by the patient data management system (NarkoData; Imeso, Gießen, Germany). In the case of a missing BP reading due to transfer of the patient into the operating room, the last measured values were carried forward. More than two missing consecutive oscillometric BP readings led to the exclusion of the patient from the study. In cases of undetectable BP due to hypotension, the oscillometric device started a new measurement automatically.
The lowest mean arterial pressure accepted in our institution was 60 mmHg (which is also the lowest safe value according to Walsh et al. 1). The latter group1 also noted that a mean arterial pressure of 55 mmHg puts a patient at risk, therefore, a difference of 5 mmHg is clinically relevant. We based our sample size calculation on the assumption of a mean difference of 5 mmHg in mean arterial pressure between the two groups, a SD of 11 mmHg, an α-error of 0.05 and a β-error of 0.2. This calculation indicated a minimum number of 160 patients with complete BP data. Completeness of data was assessed after study inclusion. The number of dropouts was compensated for by including additional patients until 160 complete data sets were available for analysis.
Patients’ characteristics and serum creatinine values were obtained from the patient data management system. Likewise, the immediate postoperative outcomes, such as unplanned transfer to an intermediate or ICU or death in hospital were obtained from this system.
For analysis of the data, Excel 2010 (Microsoft, Redmond, Washington, USA), SPSS version 23 (IBM, Armonk, New York, USA) and R version 3.3.1 (The R foundation, Vienna, Austria) were used. After screening BP recordings for erroneous readings, descriptive statistics for systolic arterial pressure, mean arterial pressure and diastolic arterial pressure were calculated. Differences in BP between the groups were tested at the different time points by using Student's t test, corrected for multiple testing by using the Bonferroni–Holm procedure.13 Testing for differences in fluid administration was also performed by using Student's t test (no indications for violations of normality assumption). Wilcoxon test was used to test differences in urine output, norepinephrine administration and changes in serum creatinine, as the data for these three values were found to be most probably not normally distributed. Quasi-binomial regression was used to test whether the frequency of hypotensive measurements differed significantly between the two groups.14 The Chi-squared test was used to test for differences between the groups with respect to the various anaesthetic combinations, the frequency of additional epidural anaesthesia and intraoperative beach chair positioning, respectively.
Figure 1 illustrates patient recruitment and dropouts: 198 patients were included in the study. Data from 33 patients were incomplete due to missing BP readings (18 in the study group and 15 in the control group). In two cases, intermittent BP data could not be recorded because of technical issues, in all other cases the missing data was due to the anaesthetist stopping BP readings to allow a second intravenous access to be established. In one patient, the ClearSight device failed to provide a waveform. The data from 160 patients were available for analysis: 77 in the study group and 83 in the control group. The patients’ characteristics are shown in Table 1.
Chi-squared testing revealed no significant differences between the groups with regard to the mix of anaesthetics, the number of patients with epidural anaesthesia or who had beach chair positioning for surgery (Table 1). A urinary catheter was present in 47 and 38 patients of study and control group, respectively.
We analysed and compared the oscillometric BP values for the first hour of general anaesthesia. One reading every 3 min resulted in 160 values for systolic, mean and diastolic arterial pressure at each of the 20 time points. The mean ± SD (range) of all these BPs were: systolic arterial pressure 128 ± 27 (47 to 234) mmHg, mean arterial pressure 96 ± 20 (34 to 191) mmHg and diastolic arterial pressure 71 ± 15 (27 to 138) mmHg. At the beginning of the anaesthesia, there was no statistically significant difference in baseline BPs between the two groups. At 12 min, the mean arterial BP values of the control group were an average of 12 mmHg lower than in the study group, 90 vs. 102 mmHg, respectively (P = 0.039) (Fig. 2b). Likewise, systolic arterial pressure was 18 mmHg less in the control than the study group, 117 vs. 135 mmHg (P = 0.015) (Fig. 2a). A statistically significant BP difference between the groups persisted for the next measurement at 15 min. With regard to relative changes in BP by 6 min after induction, the mean arterial BP had decreased in a similar manner in both groups, 16% lower in the study group and 15% lower in the control group (Fig. 2b). Although BP in the study group was stabilised after 9 min, in the control the mean BP continued to fall until 15 min when it was 19% lower than the baseline pressure (Fig. 2b). From the 21st minute onward, there were no significant differences in absolute or relative BP values between the two groups.
Hypotension occurred more often in the control group (Fig. 3), with 51 measurements of mean arterial pressure below 60 mmHg compared with 19 in the study group (P = 0.011). Mean arterial BP readings less than 55 mmHg were recorded 25 times in the control group compared with 7 in the study group (P = 0.047). Mean arterial BPs more than 140 mmHg were noted almost equally often in both groups; 44 in the study group and 38 in the control group (P = 0.667).
Although a higher cumulative total dose of norepinephrine was administered in the study group within the first hour of general anaesthesia, this difference was not statistically significant: Median (lower quartile to upper quartile) 0.23 (0.14 to 0.31) and 0.17 (0.12 to 0.27) mg in the study and control group, respectively (P = 0.061). The control group received more fluid than the study group (430 ± 169 vs. 374 ± 168 ml, respectively; P = 0.040). Urine output was higher in the study group than in the control group: 200 (100 to 350) vs. 100 (60 to 250) ml, respectively (P = 0.017). Both preoperative and postoperative serum creatinine values were available in 58 study group and 67 control group patients. There was no statistically significant difference between the groups with regard to the change between preoperative and postoperative values: change between the groups 0 (−0.1 to 0) vs. 0 (−0.1 to 0) mg dl−1, respectively; P = 0.602.
There were no immediate postoperative complications in either group and all patients were transferred to the normal ward after recovery from surgery. One patient in the control group suffered from lethal thromboembolic complications 1 week after surgery, all other patients were discharged from hospital alive.
The current study observed whether BP stability is influenced by the presence of continuous BP monitoring in orthopaedic patients with chronic hypertension undergoing routine general anaesthesia. Compared with the control group, the BP of patients who were monitored continuously was more stable, with significantly fewer hypotensive periods. As the treating anaesthetists in this study were blinded to the aim of the investigation, it would appear that, even in the absence of any specific protocol, the availability of continuous BP monitoring data resulted in hypotension being treated sooner than when only intermittent monitoring was used.
In the past, several studies showed that intraoperative hypotension can be dangerous by causing adverse outcomes, following compromised perfusion of organs.1–3 However, the definitions of intraoperative hypotension vary widely and the question ‘how low is too low?’ remains unanswered.16 On account of the changes to the pressure limits of blood flow auto-regulation in the presence of chronic hypertension, in such patients a different threshold may be required for the treatment of hypotension compared with healthy individuals.17 In the present investigation, the thresholds suggested by Walsh et al. 1 of 60 and 55 mmHg were applied. His group found a significantly higher risk of acute kidney failure as soon as mean arterial pressure was 55 mmHg or less, even for a time as short as 1 min.1 These findings have recently been confirmed by Salmasi et al. 4, who suggest an absolute lowest threshold of 65 mmHg instead of a relative reduction from baseline BP.
Continuous non-invasive BP monitoring has been shown to detect hypotension earlier than intermittent oscillometric measurement every 15 min in the emergency department.18 Continuous monitoring was able to detect hypotension significantly more often than intermittent monitoring (every 3 min) during elective caesarean section under spinal anaesthesia.19 For endoscopic procedures, compared with intermittent monitoring, Siebig et al. 20 concluded that continuous BP measurement was more favourable in terms of patient safety. In the perioperative setting, Benes et al. 21 investigated the effect of continuous non-invasive monitoring on BP stability in 40 patients undergoing surgical procedures in the beach chair position. The authors noted better BP stability when a continuous BP measurement device was used compared with intermittent monitoring. However, there are important differences regarding the design of that study21 compared with the present investigation. The treating anaesthetist in their study21 knew the purpose of the study and a specific protocol was in place to maintain systolic arterial pressure within predefined boundaries. The benefit to be expected from continuous monitoring in every day practice cannot be concluded from such a setting. Furthermore, the oscillometric measurements were performed every 5 min, a time interval between readings, which we consider to be too wide. Treating hypotension or hypertension with only one BP assessment every 5 min can very easily lead to inadequate interventions. Therefore, to conform with our normal clinical practice, we chose to leave the time interval between intermittent BP readings at our standard setting of 3 min. Also, in the current study, mean arterial pressure was regarded as the target value when defining hypotension as organ perfusion depends on an adequate mean arterial pressure rather than systolic arterial pressure.
Continuous non-invasive BP monitoring is not used commonly in every day perioperative practice, although in a study of 120 elective surgical patients, Vos et al. 22 concluded that its measurement performance was inter-changeable with oscillometric monitoring. In most patients undergoing general anaesthesia, BP is monitored by intermittent oscillometric measurements via an upper arm cuff. Although the accuracy of such intermittent oscillometric measurements has been questioned,23,24 in the absence of an intra-arterial catheter, upper arm cuff oscillometrically assessed BP has become the unofficial ‘gold standard’ in routine clinical practice.25
Data evaluating the impact of continuous BP monitoring prospectively under clinical conditions are rare. In some cases, the insertion of an arterial catheter is deemed necessary when patients undergo general anaesthesia. Reasons for such a choice are procedure-related and patient-related: procedure-related reasons include a high probability of significant blood loss, haemodynamic problems or the need of frequent blood gas analyses; patient-related reasons include serious pre-existing cardiovascular disease. In such high-risk cases, the arterial line assists the anaesthetist to maintain a stable BP. If the main function of intra-arterial BP is to stabilise BP, our data suggest that its insertion before induction of general anaesthesia makes more sense than waiting until after induction and intubations when anaesthetic drugs have already exerted their side effects on the patient's haemodynamic status. In our study, the continuously monitored patients had higher BP values. As the dose of vasopressors in this study was not significantly different between the groups, the most likely explanation for the clinically relevant difference between the two groups is that the vasopressor therapy was started earlier in the presence of continuous monitoring when BP changes could be visualised immediately. To avoid complications related to arterial cannulation, non-invasive continuous monitoring could be an option in those patients who do not need arterial blood samples but who would benefit from stable haemodynamic conditions.
Although the study group received less fluid, the median urine output after 1 h was higher compared with the control group. Again, a possible explanation for this could be that norepinephrine was given earlier in the study group before BP could decrease to values that are known to endanger kidney function.1 In the study group, with significantly fewer mean BP readings below 55 mmHg, urine output never decreased despite less infused fluid. On the contrary, the limited number of patients included in the study prevents any definite conclusions on changes in kidney function.
The main strength of our study is that it was performed under nearly normal routine clinical conditions with no imposed BP control protocols. The fact that the anaesthetist in charge did not know the real purpose of the study, rules out a potential bias caused by them in paying special attention to BP.
We cannot conclude from our data whether an intermittent BP measurement interval of less than 3 min would have the same effect as continuous monitoring. This question would need to be addressed in further research. In addition, the impact of continuous non-invasive BP monitoring established before induction of general anaesthesia needs to be investigated separately in different patient groups. Data on the benefit of continuous monitoring in different types of patients are essential before recommendations can be made as to which patients should receive an arterial line or other continuous monitoring and for which cases intermittent monitoring alone is sufficient.
We conclude that compared with patients whose BP is monitored intermittently only, in orthopaedic patients with chronic hypertension undergoing general anaesthesia under routine conditions, the presence of continuous BP monitoring contributes to maintaining a stable BP and results in fewer hypotensive episodes.
Acknowledgements relating to this article
Assistance with the study: we would like to thank Dr Bernhard Pollwein and Baocheng Wang, who were responsible for data extraction from the patient data management system.
Financial support and sponsorship: this study was funded by an institutional grant for young investigators (FöFoLe program of the faculty of medicine, LMU Munich).
Conflict of interest: ASM had received unrestricted research grants from Tensys Medical, Inc. (San Diego, California, USA) and refunds of travel expenses from CNSystems Medizintechnik AG (Graz, Austria) in the past.
Presentation: preliminary data have been presented as a poster presentation at the European Society of Anaesthesiology (ESA) Euroanaesthesia, 28 to 30 May 2016, London.
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