Keywords

Sedation; Pulmonary Vein Isolation; Respiratory acidosis; Alveolar hypoventilation; Blood gas analysis

Introduction

Pulmonary vein isolation is widely performed under procedural sedation and analgesia (PSA). PSA aims to relieve anxiety, discomfort and pain during the procedure using hypnotic and/ or analgesic medication. The hallmark of PSA is that spontaneous breathing and a patent airway are preserved despite a depressed level of consciousness. During PSA, the depth and rate of ventilation are decreased because of depression of respiratory control centres [1]. This can leads to alveolar hypoventilation, resulting in an increased arterial CO₂ levels and respiratory acidosis [2, 3]. Acidosis can lead to myocardial suppression and arrhythmias [4]. Practice guidelines advise the use of capnography to facilitate early detection of respiratory depression [1, 5]. The use of capnography greatly enhances the safety of PSA by warning of respiratory complications [6].

However, capnography during PSA is not an accurate technique for detecting hypercapnia because there is considerable mixing of room air in the sampling when not using an endotracheal tube. The gold standard for assessing respiratory status remains arterial blood gas analysis [2]. Although there are no obvious adverse effects of short-term respiratory acidosis, it is not a physiologically normal condition. This study aims to investigate the degree of respiratory depression and resulting respiratory acidosis over time in routine pulmonary vein isolation procedures.

Methods

This single centre prospective observational study was performed at the cardiac catheterization unit of the Radboud University Medical Centre, Nijmegen, The Netherlands. Ethical approval for this prospective observational study was given by the Medical Ethical Committee CMO Arnhem-Nijmegen, The Netherlands (chairperson R. Dekhuijzen) on May 9, 2019 (METC nr 2019- 5211). All the procedures were performed in accordance with the Declaration of Helsinki.

Patients

Patients eligible for this study were all adult patients that were scheduled for pulmonary vein isolation under PSA. Patients were consecutively included between October 2019 and September 2020. Exclusion criteria were ASA classification 3 or higher, body mass index over 30 or under 18, age above 80, having been diagnosed with obstructive sleep apnoea syndrome, COPD or asthma or known bleeding disorders. Inclusions stopped after reaching 20 participants.

Study protocol

Patients were included after written informed consent. Before the start of the procedure, we inserted an intravenous cannula. Throughout the procedure patients were monitored with pulse oximetry, non-invasive arterial blood pressure measurements and continuous ECG. In addition an arterial cannula was placed in all patients. These were placed in the radial artery under local anaesthesia and ultrasound guidance by a physician or a physician assistant. The PSA was provided by a qualified physician assistant, under supervision of an anaesthesiologist. Before starting PSA, low-flow supplemental oxygen delivery was started through a nasal cannula with a side port allowing CO₂ sampling. EtCO₂ and the capnography waveform were monitored throughout the procedure for early detection of changes in ventilation.

For PSA we used propofol and remifentanil in a dose range of 4-8 mg.kg.hr^-1 and 0.01 – 0.05 μg.kg.min^-1 respectively. No other sedatives were administered. The PSA depth was estimated using the Ramsay sedation scale and maintained at 5-6 [7,8]. Upper airway obstruction was managed with manual airway manoeuvres, placement of an oral pharyngeal airway (OPA) device or nasal pharyngeal airway (NPA) device. If apnoea persisted despite a patent airway, PSA depth was reduced and ventilation was supported through facemask ventilation until spontaneous breathing recovered.

The data recorded included patient characteristics, the start and end times of PSA (determined as starting and stopping of propofol infusion) and arterial blood gas analyses. Blood gas analysis was performed before starting PSA, and every 30 minutes during the PSA. At the end of the PSA, a sample was taken at the moment propofol was stopped, and after 30 and 60 minutes.

The recorded blood gas values were pH, pCO₂, pO₂, HCO₃ -, base excess and lactate. Other data recorded were heart rate (HR), blood pressure (BP) and oxygen saturation as measured by pulseoximeter (SpO₂). All blood gas measurements were made using a point-of-care analyser (i-STAT, Abbott, CG4+-cartridges).

Statistical analysis

The primary outcome of this study was the change in arterial CO₂ over time compared to baseline measurement during prolonged PSA. Secondary outcomes were changes in arterial pH and other blood gas parameters. Data are expressed as mean ± SEM, or median [range], depending on their distribution. Differences over time between groups were analysed with repeated measures two-way analysis of variance (ANOVA), providing that data were normally distributed. In the case of non-normally distributed data, we compared the area’s under the concentration-time curve using Mann-Whitney U tests. Differences in group means or medians were tested with Student’s t-tests for parametric data or Mann-Whitney U tests for non-parametric data. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, N.Y., USA) and Graph pad Prism, version 5.03 for Windows (GraphPad Software, San Diego California USA, www.graphpad.com).

Results

Demographic data are presented in Table 1.

Twenty patients were included in the study. All patients underwent an uneventful pulmonary vein isolation procedure. Procedure times varied considerably with a median of 50 [30- 290] minutes. In most patients (85%) the procedures took 80 minutes or less, while in 3 patients, procedure times were much longer [122 - 290 minutes]. All patients awoke promptly after propofol and remifentanil administration were ceased, irrespective of the duration of the procedure. At the time of the intraoperative blood gas analysis, all patients had a Ramsay score of 5-6. We were able to maintain an open airway at all time and no persistent apnoea was observed.

Table 1 Baseline characteristics of patients undergoing pulmonal vein isolation under PSA.

The concentration of arterial CO₂ increased significantly within 30 minutes from 4.81 ± 0.66 kPa at the start of PSA to 7.13 ± 0.84 kPa at t=30 min [Figure 1]. After that no further increase in CO₂ was observed. In the 3 patients with extended procedure times, no increase was noted compared with t=30 min. No correlation was found between procedure time and arterial CO₂ at the end of the procedure (Spearman r = 0.33, P = 0.19). In addition, no correlation was found between remifentanil or propofol dose and CO₂ at T=30 and T=60 minutes. After cessation of PSA, CO₂ normalized to baseline with 30 minutes.

Figure 1 PaCO₂ over time. PaCO2 over time.

As expected, pH decreased proportionally, from 7.43 ± 0.06 at baseline to 7.29 ± 0.03 at t=30 min, and remained stable throughout the procedure until the end of the PSA. There was a good correlation between arterial CO₂ and pH (Spearman r = -0.87) indicating that acidosis was primarily caused by respiratory depression [Figure 2].

Other blood gas parameters are displayed in table 2, dosages of medication are displayed in Table 3.

Table 2 Blood gas analyses throughout PSA.

Table 3 Dosages of medication throughout PSA.

Figure 2 Correlation between arterial CO₂and pH.

Discussion

This prospective observational study shows a significant increase in arterial CO2 levels in pulmonary vein isolation performed under PSA. This hypercapnia resulted in a respiratory acidosis in all patients and which remained constant throughout the procedure. During PSA, airway patency was maintained by routine use of oropharyngeal airways, and capnography was used to detect any airway obstruction. The increased PaCO2 was therefore due to a decreased depth and rate of ventilation by depression of respiratory control centres.(1) CO2 levels rose and stabilized after 30 minutes indicating a new setpoint in the respiratory control centre. This is in concordance with a previous study in which a statistically significant PaCO2 increase was shown as soon as 5 minutes after starting PSA levelling off after 10 minutes [3].

During PSA, EtCO2 monitoring is advised to monitor ventilation in order to prevent unnoticed CO2 retention[3]. In this study, we demonstrated that CO2 retention is present in all patients during pulmonary vein isolation under PSA, also in patients with a patent airway who are breathing spontaneously throughout the procedure. A PaCO2 > 6 kPa is common during PSA[9]. It occurs more often in patients who receive supplemental O2[10]. The degree of CO2 increase depends on the depth of the sedation and the sedatives used. A previous study in patients under moderate or conscious sedation (Ramsey sedation score of 3) showed that sedation with dexmedetomine and fentanyl or remifentanil resulted in a median PaCO2 of 5.32 [4.80-6.00] kPa, whereas patients sedated using propofol had a PaCO₂ of 5.86 [5.33-6.53] kPa.(11, 12) When a combination of fentanyl and midazolam was used to achieve a Ramsey sedation score of 3, PaCO2 reached levels between 5.5 and 7 kPa.(10) In our study, PaCO2 increased to 7.13 ± 0.84 kPa, which is likely due to a deeper level of sedation in this study, corresponding with a Ramsey score of 5 to 6. Regardless of the duration of the procedure and PaCO2 concentration, postprocedural arterial blood gas values in our patients normalized within 30 minutes after stopping propofol infusion.

The hypercapnia during the procedure had no apparent negative consequences for the patients in this study. The effects of permissive hypercapnia in critically ill patients with severe respiratory failure are well described [13], but to our knowledge there has been no previous research into the effects of shortterm hypercapnia and acidosis.

Limitations of our study include the single-centre prospective observational study design. Furthermore, the physician assistants who administered the sedation were not blinded to the results although the results did not lead to any change in the PSA. Only three patients underwent an extended PSA procedure, the majority of the procedures were completed within 90 minutes. The interval between measurements chosen is too large to indicate precisely how fast the new respiratory equilibrium is reached and how fast the patient recovers from the hypercapnia after the procedure. Finally, patients with respiratory problems such as obstructive sleep apnoea syndrome, COPD or asthma, were excluded from our study, but further research into the effects of PSA on the respiratory drive is warranted to assess the safety of deep PSA in these patients.

Conclusion

During pulmonary vein isolation procedures performed with PSA a significant increase in CO2 levels was found. This hypercapnia resulted in a respiratory acidosis in all patients, which stabilized within 30 minutes. Longer procedure times did not lead to higher CO2 levels.

During pulmonary vein isolation procedures performed with PSA a significant increase in CO2 levels was found.

Declarations

Availability of data

Data is available on request from the authors.

Funding

Departmental funding only

Conflicts of interest: None to declare.

References

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