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DOI: 10.1055/s-0028-1119671
© Georg Thieme Verlag KG Stuttgart · New York
Sedation with propofol for interventional endoscopy by trained nurses in high-risk octogenarians: a prospective, randomized, controlled study
D. SchillingMD, PhD
Diakoniekrankenhaus Mannheim
Speyererstrasse 91 – 93
68163 Mannheim
Germany
Fax: +49-621-81023410
Email: D.schilling@diako-ma.de
Publication History
submitted5 June 2008
accepted after revision29 December 2008
Publication Date:
01 April 2009 (online)
Background and study aims:Sedation with the short-acting anesthetic agent propofol has shown several advantages, particularly in interventional endoscopy. So far, however, there are no valid data on the safety of nurse-administered propofol sedation (NAPS) during interventional endoscopy in elderly high-risk patients.
Patients and methods:A total of 150 patients aged > 80 years with high comorbidity were randomized to receive midazolam plus meperidine (n = 75) or propofol alone (n = 76) for sedation during endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), or double-balloon endoscopy (DBE). Sedation was supervised by a trained nurse and a trained physician both of whom were not involved in the endoscopic procedure. Vital signs were continuously monitored as well as patient cooperation and tolerance. Mortality and morbidity at 30 days was analyzed.
Results:The overall cardiopulmonary complication rate was 16 % in the midazolam group and 23.7 % in the propofol group (P > 0.05). The mean decline in oxygen saturation (initial vs. lowest O2 saturation) and the mean decline of blood pressure (initial vs. lowest blood pressure) were significantly greater with propofol (7 % ± 3 % vs. 4 % ± 2 % [P < 0.05] and 10 % ± 2 % vs. 8 % ± 2 %, respectively [P < 0.05]). No procedure had to be interrupted due to serious adverse events. Patient cooperation was statistically significantly better in the propofol group (7 ± 2 vs. 5 ± 2 points). Patients sedated with propofol showed a significantly lower oxygen saturation rate during recovery time (8 % vs. 28 %; P ≤ 0.01).
Conclusion:NAPS during interventional endoscopy is as safe as midazolam/pethidine sedation even in high-risk patients aged > 80 years.
#Introduction
Recent studies on large patient populations have proved the superiority of propofol sedation over benzodiazepines and opioids for sedation during interventional endoscopy [1] [2]. Because of its shorter onset time and faster recovery time, propofol seems to be the ideal medication for interventional endoscopy. One disadvantage of propofol is the risk of rapid change from conscious sedation to deep sedation or even general anesthesia with resultant cardiopulmonary depression. Another disadvantage is that there is no antagonist. Therefore, anyone administering propofol must be trained in emergency medicine in order to manage cardiopulmonary depression. The administration of propofol by anesthesiologists increases the costs associated with endoscopic procedures. In the USA and Switzerland, nurse-administered propofol sedation (NAPS) with supervision by the gastroenterologist was introduced some years ago with excellent results [3] [4] [5]. Recently, similar results were reported by German groups who analyzed the safety of NAPS in outpatient gastroenterology clinics [5].
Interventional endoscopy in patients older than 80 years will increase in future years due to the demographic development of Western countries. Recent studies have demonstrated that, under careful monitoring, the use of propofol during endoscopic retrograde cholangiopancreatography (ERCP) is superior to midazolam/meperidine or pethidine sedation, even in high-risk octogenarians [6] [7]
Cost aspects have prompted the search for a less-expensive approach without losing the quality of a clinic setting. We therefore examined NAPS in high-risk octogenarians during interventional endoscopic procedures in a prospective, randomized study, comparing the conventional sedation midazolam/pethidine with propofol sedation.
#Methods
#Protocol
A total of 157 consecutive patients aged 80 years or older who were admitted to our hospital for ERCP, endoscopic ultrasound (EUS), or double-balloon enteroscopy (DBE) from March 2006 to June 2007 were included in the study. Patients from whom consent was not obtained were excluded.
All patients were randomly assigned to one of the three different interventions by a computer-generated list by an independent physician. All patients were classified according to the American Society of Anesthesiologists (ASA). Most patients were classified as ASA Class III (severe systemic diseases that are not incapacitating).
#Sedation, monitoring, and assessed parameters
The endoscopic procedures were performed by experienced investigators (DS, HR), using standard techniques with the patient positioned in the prone position during ERCP and positioned on the left side during DBE and EUS. Therapeutic duodenoscopes (TJF 160 R and VR, Olympus Optical, Hamburg Germany), EUS with longitudinal scanner (Pentax FG 34Ux Pentax Europe GmbH, Hamburg Germany), and a therapeutic double-balloon enteroscope (EN-450T5/W Fujinon Europe GmbH Willich) were used.
Heart rate, electrocardiogram (ECG), oxygen saturation, and blood pressure were monitored throughout the procedure and for 2 hours after the procedure (Dash 300, Marquette GmbH, Freiburg Germany). All patients received at least 500 mL of saline infusion and a continuous oxygen supplementation of 3 L/min.
Sedation was initiated by physicians who were not involved in the endoscopic procedure and who were experienced in intensive care medicine and resuscitation. After initiation patients were supervised by trained nurses under the supervision of physicians. Every physician had performed more than 100 propofol sedations. Nurses were trained for 3 days (February 2006) on various topics, including advanced life support, airway management with mask ventilation and intubation, analysis of ECG monitoring, and didactic training on the effects of propofol. The supervising physicians documented the need for intervention due to iatrogenic events.
The physician-controlled NAPS was initiated in our department 4 weeks before the study started in order to collect experience.
The following parameters were assessed: decrease of heart rate < 50 bpm, oxygen saturation < 90 %, systolic blood pressure < 90 mmHg, and changes in heart rhythm. As described in the study of Riphaus et al. [6], we selected the oxygen decrease < 90 % as the strongest risk factor.
The main outcome measure was the rate of cardiopulmonary events. A second outcome measure was the need for additional intervention in case of adverse events.
#Definition of adverse cardiopulmonary events
A serious adverse event was defined as an episode of apnea requiring assisted ventilation, cardiac arrest requiring resuscitation, or bradycardia ≤ 50 bpm requiring drug therapy. A minor event was defined as desaturation of oxygen < 90 % over a period of < 30 seconds with a spontaneous return to normal.
In cases of oxygen saturation below 90 %, nasal inflow of oxygen was increased to 4 – 6 L/min. In the midazolam group, antagonists of midazolam or meperidine were given if saturation of oxygen declined to 85 % or less. Mask ventilation and interruption of the examination were initiated in both groups if it seemed to be necessary.
In the midazolam group sedation was induced by an intravenous bolus of 2.5 – 3.0 mg of midazolam (Midazolam ratiopharm, Ulm, Germany) and a bolus of 25 – 50 mg pethidine (Dolantin, Aventis Frankfurt, Germany). Repeated doses were given by the nurse under the supervision of the physician, to ensure adequate sedation.
In the propofol group, repeated doses of 20 mg propofol were administered (Braun, Melsungen) after a loading dose of 40 mg (< 70 kg body weight) or 60 mg (> 70 kg body weight) was injected.
Patient cooperation was scaled on a visual analog scale from 0 points (no cooperation) to 10 points (excellent cooperation) by the endoscopist.
#Follow-up
After the endoscopic procedure patients were monitored over a period of 2 hours without oxygen supplementation. The rate of oxygen desaturation during the recovery phase was examined. Thereafter, all patients were clinically supervised as inpatients for at least one night. All patients were observed for another 72 hours to evaluate the clinical course.
The data of 30-day morbidity and mortality were collected and analyzed.
#Statistics
Sample size was calculated under the assumption that the cardiopulmonary complication rates of standard sedation and propofol are 17 %. These data are the result of a meta-analysis of 12 original studies that assessed the cardiopulmonary complications of propofol sedation compared with standard regimens [1]. In order to prove equivalence of both regimens with a pre-specified equivalence limit of 15 % for complication rate with an alpha value of 5 % and a power of 80 %, a sample size of 78 patients per group was necessary (one-sided test). All data were given as mean ± SD.
Baseline data, diagnoses, and endoscopic procedures were compared with the Mann–Whitney U test, chi-squared test and Student’s t-test whenever appropriate. The equivalence of event rates was proven using the confidence interval of the odds ratio. For all statistical calculations, a P-value of less than 0.05 was considered to be statistically significant. Data were calculated using the SPSS for Windows 13.01 software package (SPSS Chicago, Illinois, USA).
#Results
A total of 151 patients were randomized (75 patients into the midazolam/meperidine group and 76 patients into the propofol group). Two patients from the midazolam/meperidine group and three patients from the propofol group were not included because of failed duodenal intubation.
There were no significant differences between the two groups with regard to age, sex, ASA classification, type of endoscopic intervention, or special characteristics that might influence patient cooperation under sedation (e. g. alcohol use, use of analgesic medication) ([Tables 1 3]).
| Midazolam n = 75 |
Propofol n = 76 |
P-value | |
| Age, years (range) | 83.2 (80 – 96) | 82.4 (80 – 92) | > 0.05 |
| Sex, M/F | 26/49 | 25/51 | > 0.05 |
| ASA III | 38 | 34 | > 0.05 |
| ASA IV | 15 | 12 | > 0.05 |
| Alcohol use, n | 16 | 14 | > 0.05 |
| Analgesic use, n | 19 | 22 | > 0.05 |
| Midazolam n = 75 |
Propofol n = 76 |
P-value | |
| Benign bile duct stricture | 3 | 5 | > 0.05 |
| Bile duct stone | 24 | 22 | > 0.05 |
| Exclusion of bile duct stones | 10 | 8 | > 0.05 |
| Cholangiocarcinoma | 3 | 2 | > 0.05 |
| Pancreatic cancer | 10 | 12 | > 0.05 |
| Angiodysplasia of the small bowel | 0 | 2 | > 0.05 |
| Ulcer in the small bowel | 2 | 1 | > 0.05 |
| Pancreatic duct stones | 2 | 0 | > 0.05 |
| Drainage of pancreatic pseudocysts | 6 | 5 | > 0.05 |
| Midazolam (n = 75) |
Propofol (n = 76) |
P-value | |
| ERCP | 53 | 58 | > 0.05 |
| EUS | 19 | 15 | > 0.05 |
| DBE | 3 | 3 | > 0.05 |
| DBE, double-balloon endoscopy; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound. |
The mean dosage was 6 mg (2 – 8 mg) for midazolam, 50 mg (25 – 100 mg) for pethidine, and 376 mg (60 – 870 mg) for propofol. The mean examination time was 47 ± 16 minutes in the midazolam group and 42 ± 18 minutes in the propofol group (P = n. s.).
The overall cardiopulmonary complication rate was 16.0 % in the midazolam group and 23.7 % in the propofol group (P > 0.05; [Table 4]). Therefore, equivalence could not be proven. Additional intervention was not necessary in either group.
| Event | Midazolam n = 75 |
Propofol n = 76 |
| Apnea | 0 | 0 |
| Minor events of hypoxemia, n (%) | 7 (9.3) | 9 (11.8) |
| Bradycardia, n (%) | 3 (4) | 5 (6.5) |
| Arterial hypotension, n (%) | 2 (2.6) | 4 (5.2) |
| Interruption of procedure due to adverse event | 0 | 0 |
The mean decline in oxygen saturation (initial vs. lowest O2 saturation) was significantly greater with propofol compared with midazolam (7 % ± 3 % vs. 4 % ± 2 % [P < 0.05]) as was the mean decline in blood pressure (initial vs. lowest blood pressure: 10 % ± 2 % vs. 8 % ± 2 % [P < 0.05]).
Minor events of oxygen desaturation occurred more often in the propofol group but were not statistically significant (9.3 % vs. 11.8 %). All necessary interventions were managed by trained nurses (e. g. increasing the oxygen supply, lifting the jaw). In no case was the examination interrupted. Patients sedated with propofol showed a significantly lower oxygen saturation rate during the recovery period (8 % vs. 28 %; P = < 0.01). Patient cooperation was statistically significant better in the propofol group (7 ± 2 points vs. 5 ± 2 points).
The follow-up of 30 days and results from a standardized interview conducted by the endoscopists showed no variation between the two sedation groups. Two patients from the midazolam group and one patient from the propofol group died during the follow-up period from non-sedation-related events. Rehospitalization was necessary for five patients from each group due to existing or newly developed comorbidity.
#Discussion
Due to changing demographics, more sophisticated interventional endoscopic procedures will become increasingly necessary for elderly patients with a high comorbidity. To date, there have been only a few trials of elderly comorbid patients [6] [7] [8]. Some interventional procedures (e. g. stent insertion in malignant bile duct stenosis, interventional DBE) can take 1 hour or more, which is not acceptable without adequate sedation. Propofol sedation during ERCP (as an example of a lengthy interventional procedure) has been proven to be a safe form of sedation that is well accepted by patients and physicians [9] [10] [11]; however, only the trial by Riphaus et al. has analyzed the safety of propofol sedation during therapeutic endoscopy in a patient group aged 80 years or older [6]. The authors examined the safety of propofol in ERCP procedures in octogenarians and found it superior to midazolam sedation. This is in accordance with our results, despite our inclusion of other long-acting interventional procedures in addition to ERCP procedures. We found a significantly higher decrease in blood pressure and a higher oxygen desaturation rate with propofol but there was no difference in the rate of interventions due to major adverse events.
In Germany a published legal document by law states that propofol sedation has to be initiated by a physician trained in intensive care medicine, and the ongoing sedation may only be carried out by trained nurses when supervised by a physician [12]. The main side effects of propofol sedation are the respiratory depression and the arterial hypertension. In a meta-analysis, propofol sedation was associated with a lower rate of cardiopulmonary complications than midazolam in colonoscopy, whereas in the endoscopic procedures, the risk was similar to midazolam [1]. The safety of NAPS in diagnostic endoscopy of the upper or lower gastrointestinal tract is well documented in studies from the USA and Switzerland [3], and recently also by German data in outpatient colonoscopy [5]. To our knowledge this is the first prospective randomized report of the safety of NAPS in interventional endoscopy in German patients aged 80 years or older with comorbidity. As stated by law, the sedation was initiated by physicians trained in emergency medicine and then monitored by trained nurses. The physician remained in the room for the procedure and was able to manage any complications. In our study, an intervention by the physician was not necessary. Contrary to other trials, we routinely recorded ECG output in order to detect any cardiac complication in its early stage. We found no difference in arrhythmias or brady- or tachycardias between the two sedation groups.
A further important study on the safety of NAPS, is the prospective study by Tohda et al. [13], which evaluated the efficacy and safety of NAPS during emergency upper endoscopy for gastrointestinal bleeding. A total of 120 patients with acute upper gastrointestinal bleeding received propofol sedation by a trained nurse. Among these, 15 patients were classified as ASA class IV, 84 patients as class III, and 21 patients as class II. The control group consisted of 120 patients without acute gastrointestinal bleeding, who underwent upper endoscopy during the study period. None of the patients required assisted ventilation by a bag mask. No sedation-related deaths or serious complications were reported, even in high-risk patients, 44 % of whom were aged > 70 years.
The proportion of elderly people in this study particularly reflects the demographic development of an increasing number of elderly people with high comorbidity rates but needing interventional endoscopic procedures. However, the safety and efficacy of propofol sedation has been evaluated in only small patient series.
The use of propofol sedation is more costly than midazolam sedation because of increased direct costs of medication and necessary infusion, as well as indirect costs associated with the additional staff required. In this context it is important to prove the safety of NAPS in order to be more financially efficient. NAPS in elderly patients with comorbidity enables interventional endoscopists to provide an advantage without raising the costs. Our study indicates that NAPS is safe for interventional endoscopy in patients older than 80 years, even if equivalence for both regimens was not proven with respect to cardiovascular complication rate. However, no procedure was interrupted due to major adverse events; only minor adverse events occurred. Furthermore, the low complication rate during the recovery phase and the statistically better patient cooperation makes NAPS a good alternative to standard regimens.
Our data are only the results of a single-center study and it might not be possible to generalize our findings. If these findings can be confirmed in larger multicenter studies, they could have an important impact on guidelines for sedation during interventional endoscopy. In this context, it must be mentioned that interventional endoscopy is performed in hospitals, where a trained physician is able to intervene rapidly in cases of adverse events.
Because single-use material is costly, we did not use other techniques for respiratory control, such as capnography. The use of capnography is not recommended in the American or German guidelines. However, more intensive technical monitoring may be able to improve the safety of NAPS, which then reduces the cost of additional staff members.
In conclusion, our study shows that a well-trained team is able to perform NAPS during interventional endoscopy in a safe environment. This is well accepted by both patients and physicians. Multicenter trials are required to confirm these findings.
#Acknowledgment
We thank S. Schneider, Institute of Research in Myocardial Infarction, Ludwigshafen, Germany for his statistical support.
Competing interests: None
#References
- 1 Qadeer M A, Vargo J J, Khandwala F. et al . Propofol versus traditional sedative agents for gastrointestinal endoscopy: a meta-analysis. Clin Gastroenterol Hepatol. 2005; 3 1049-1056
- 2 Heuss L T, Schnieper P, Drewe J. et al . Safety of propofol for conscious sedation during endoscopic procedures in high-risk patients – a prospective, controlled study. Am J Gastroenterol. 2003; 98 1751-1757
- 3 Rex D K, Heuss L T, Walker J A. et al . Trained registered nurses/endoscopy teams can administer propofol safely for endoscopy. Gastroenterology. 2005; 129 1781-1782
- 4 Heuss L T, Schnieper P, Drewe J. et al . Risk stratification and safe administration of propofol by registered nurses supervised by the gastroenterologist: a prospective observational study of more than 2000 cases. Gastrointest Endosc. 2003; 57 664-671
- 5 Sieg A. Propofol sedation in outpatient colonoscopy by trained practice nurses supervised by the gastroenterologist: a prospective evaluation of over 3000 cases. Z Gastroenterol. 2007; 45 697-701
- 6 Riphaus A, Stergiou N, Wehrmann T. Sedation with propofol for routine ERCP in high-risk octogenarians: a randomized, controlled study. Am J Gastroenterol. 2005; 100 1957-1963
- 7 Heuss L T, Schnieper P, Drewe J. et al . Conscious sedation with propofol in elderly patients: a prospective evaluation. Aliment Pharmacol Ther. 2003; 17 1493-1501
- 8 Lee D W, Chan A C, Sze T S. et al . Patient-controlled sedation versus intravenous sedation for colonoscopy in elderly patients: a prospective randomized controlled trial. Gastrointest Endosc. 2002; 56 629-632
- 9 Wehrmann T, Kokabpick S, Lembcke B. et al . Efficacy and safety of intravenous propofol sedation during routine ERCP: a prospective, controlled study. Gastrointest Endosc. 1999; 49 677-683
- 10 Hofmann C, Kiesslich R, Brackertz A. et al . Propofol for sedation in gastroscopy – a randomized comparison with midazolam. Z Gastroenterol. 1999; 37 589-595
- 11 Koshy G, Nair S, Norkus E P. et al . Propofol versus midazolam and meperidine for conscious sedation in GI endoscopy. Am J Gastroenterol. 2000; 95 1476-1479
- 12 Ehlers A PF, Bitter H. Delegation of propofol administration to non physican staff. Endosk heute. 2006; 2 139-143
- 13 Tohda G, Higashi S, Sakumoto H. et al . Efficacy and safety of nurse-administered propofol sedation during emergency upper endoscopy for gastrointestinal bleeding: a prospective study. Endoscopy. 2006; 38 684-689
D. SchillingMD, PhD
Diakoniekrankenhaus Mannheim
Speyererstrasse 91 – 93
68163 Mannheim
Germany
Fax: +49-621-81023410
Email: D.schilling@diako-ma.de
References
- 1 Qadeer M A, Vargo J J, Khandwala F. et al . Propofol versus traditional sedative agents for gastrointestinal endoscopy: a meta-analysis. Clin Gastroenterol Hepatol. 2005; 3 1049-1056
- 2 Heuss L T, Schnieper P, Drewe J. et al . Safety of propofol for conscious sedation during endoscopic procedures in high-risk patients – a prospective, controlled study. Am J Gastroenterol. 2003; 98 1751-1757
- 3 Rex D K, Heuss L T, Walker J A. et al . Trained registered nurses/endoscopy teams can administer propofol safely for endoscopy. Gastroenterology. 2005; 129 1781-1782
- 4 Heuss L T, Schnieper P, Drewe J. et al . Risk stratification and safe administration of propofol by registered nurses supervised by the gastroenterologist: a prospective observational study of more than 2000 cases. Gastrointest Endosc. 2003; 57 664-671
- 5 Sieg A. Propofol sedation in outpatient colonoscopy by trained practice nurses supervised by the gastroenterologist: a prospective evaluation of over 3000 cases. Z Gastroenterol. 2007; 45 697-701
- 6 Riphaus A, Stergiou N, Wehrmann T. Sedation with propofol for routine ERCP in high-risk octogenarians: a randomized, controlled study. Am J Gastroenterol. 2005; 100 1957-1963
- 7 Heuss L T, Schnieper P, Drewe J. et al . Conscious sedation with propofol in elderly patients: a prospective evaluation. Aliment Pharmacol Ther. 2003; 17 1493-1501
- 8 Lee D W, Chan A C, Sze T S. et al . Patient-controlled sedation versus intravenous sedation for colonoscopy in elderly patients: a prospective randomized controlled trial. Gastrointest Endosc. 2002; 56 629-632
- 9 Wehrmann T, Kokabpick S, Lembcke B. et al . Efficacy and safety of intravenous propofol sedation during routine ERCP: a prospective, controlled study. Gastrointest Endosc. 1999; 49 677-683
- 10 Hofmann C, Kiesslich R, Brackertz A. et al . Propofol for sedation in gastroscopy – a randomized comparison with midazolam. Z Gastroenterol. 1999; 37 589-595
- 11 Koshy G, Nair S, Norkus E P. et al . Propofol versus midazolam and meperidine for conscious sedation in GI endoscopy. Am J Gastroenterol. 2000; 95 1476-1479
- 12 Ehlers A PF, Bitter H. Delegation of propofol administration to non physican staff. Endosk heute. 2006; 2 139-143
- 13 Tohda G, Higashi S, Sakumoto H. et al . Efficacy and safety of nurse-administered propofol sedation during emergency upper endoscopy for gastrointestinal bleeding: a prospective study. Endoscopy. 2006; 38 684-689
D. SchillingMD, PhD
Diakoniekrankenhaus Mannheim
Speyererstrasse 91 – 93
68163 Mannheim
Germany
Fax: +49-621-81023410
Email: D.schilling@diako-ma.de