Sedation by Propofol for Painful Care Procedures at the End of Life: A Pilot Study. PROPOPAL 1

Abstract

Background:

At the end of life, patients may feel refractory pain during care procedures although they receive appropriate analgesia. They can benefit from a short-term sedation. Propofol is used for procedural sedation in emergency or reanimation departments. It may be adapted in a palliative care unit.

Objective:

The main objective was to verify whether propofol could allow us to administer care without causing major pain to patients with refractory pain at the end of life.

Design:

We conducted an open, prospective, and uncontrolled pilot study.

Setting/Subjects:

The study was conducted in one palliative care center in France. The subjects were patients with an estimated prognosis less than three months who experienced pain during care procedures, although they receive appropriate analgesia.

Results:

Ten patients were included. Care was delivered with no major pain for 9 patients out of 10. The average duration of induction to reach deep sedation was 4 minutes (2–8) and of care procedures was 13 minutes (7–32). On average, the patient woke up 11.5 minutes after we stopped injecting propofol (7–18). Only one patient experienced a significant adverse effect caused by propofol, but it did not have any harmful consequence except the interruption of care procedures.

Conclusion:

Transitory sedation using propofol for terminally ill patients hospitalized in a palliative care unit can offer optimal comfort during painful care procedures without significant complications. Patients woke up quickly. Further studies will have to be conducted to verify these initial results and make sure there are no major drawbacks.

Introduction

At the end of life, some patients feel pain during care procedures despite receiving appropriate analgesia.¹ Such patients would therefore benefit from a short-term procedural sedation administered during procedures. We found that propofol is an appropriate sedative in those cases. Propofol is a narcotic with a rapid onset (less than a minute) and a short duration of action (a few minutes for a single dose injection).² Currently, in palliative care, propofol is used for continuous sedation,^3,4 whereas in the areas of emergency medicine and anesthesia, it is used for procedural sedation.^5,6 The aim of our study was to determine whether propofol is suitable for patients hospitalized in a palliative care unit who experience refractory pain during care procedures.

Methods

Study design

We conducted an open, prospective, and uncontrolled pilot study in one palliative care center.

The main objective was to verify whether propofol could allow us to administer care without causing major pain to patients with refractory pain.

The study was approved by the Ethical Research Committee and the French Agency for Safety of Health Products.

Setting and participants

The study was conducted at the palliative care unit of the Centre Hospitalier Universitaire de Nice (France), which treats ∼230 patients each year. The average length of stay was 15 days. The death rate was 80%.

Inclusion criteria included estimated prognosis less than 3 months, pain experienced during care procedures, and refractory to transmucosal fentanyl and equimolar mixture of oxygen and nitrous oxide (pain was defined as ≥3/10 on a Numeric Rating Scale or >2 on the Algoplus scale for patients with inability to communicate verbally⁷), age: 18 and above, consent signed beforehand by the conscious patient or by his or her trusted person for patients with cognitive impairments or unconscious patients.

Exclusion criteria included hypersensitivity to soy and egg lecithin, decompensated respiratory failure defined as a respiratory failure causing disorders of consciousness, shock, or lack of venous access.

Procedure

Indication of procedural sedation was agreed upon after collegial consultation and evaluation of the benefit risk balance.

We administered propofol after a set procedures developed in our department. The method used was flow injection titration with intravenous (IV) infusion and the dosage was 20 mg/kg/hour. The targeted depth of sedation was defined as the absence of verbal contact and eyelash reflex and was sought every minute after propofol was first administered. As soon as the targeted level of sedation was reached, the injection flow of propofol was reduced to 6 mg/kg/hour. If the patients woke up, the initial injection flow was used again until they had reached the targeted level of sedation. In case of an incident, we had to discontinue the injection of propofol. The injection was stopped as soon as the painful care procedures were completed. The patients were monitored until they woke up and had returned to their previous states. For safety reasons during this pilot study, an anesthesiologist was present for each inclusion. An assistant timed the duration of initial titration, care procedures, and wake up.

Study assessments

After the care procedure, the nurse answered the question, “was the care procedure administered without any major pain for the patient?” with “yes” or “no.” The quality of care was retrospectively measured by the nurse on a scale of 1 to 10 (10 = excellent quality). The patient retrospectively assessed his or her level of comfort during care procedures on a scale of 1 to 10 (10 = optimal comfort). We measured duration of initial titration, care procedures, and wake up as well as propofol doses and side effects. Age, pathology, treatments, blood pressure before procedure, type of painful care procedure, and cause of pain were also noted.

Results

The duration of the study was 15 months. Ten patients—seven women and three men—were included, with an average age of 67 years (range: 44–89). Nine had cancer and one had a peripheral artery disease. All patients had a normal blood pressure except for two with 70/50 and 95/70 mm Hg. Before the study, all patients were treated with basic opioids: injected fentanyl in eight cases and sufentanil in two cases. Four patients additionally received ketamine and five received midazolam as an anxiolytic. Painful care procedures were related to bed bathing in nine cases and bandaging in five cases. The main cause for pain was a pathological fracture in four cases, bone metastases in one case, painful wounds in two cases, gangrene in one case, radiation therapy-induced anus inflammation in one case, and persistent neuropathic pain in one case.

Care was delivered with no major pain for 9 patients out of 10. The quality of care was assessed by the caregiver: 10/10 for eight patients, 9/10 for one patient, and 8/10 for another patient. One patient could not be administered care because of adverse effects. Five patients were able to retrospectively assess the level of comfort they experienced during care procedures: 10/10 for four patients and 9/10 for one patient. One patient reported he had felt pain during care procedures and gave a score of 2/10. The mean duration of induction to reach deep sedation was four minutes (range: 2–8). The mean induction dose was 67 mg (range: 40–100). The mean duration of care procedures was 13 minutes (range: 7–32). The mean dose of propofol used during care procedures was 69 mg (range: 28–105). The mean total quantity of propofol used during the procedure was 131 mg (range: 58–195). For no patients did we increase the flow while care was administered. On average, the patient woke up 11.5 minutes after we stopped injecting propofol (range: 7–18).

One patient experienced a significant adverse effect caused by propofol but this effect did not have any lasting consequence except the interruption of care procedures. The patient was an 86-year-old female with refractory pain due to a peripheral artery disease and gangrene lesions. Her blood pressure was 129/58 mm Hg and her heart rate was 81 beats per min. She did not experience any respiratory distress before the procedure. The induction phase lasted 2 minutes and 30 seconds. Immediately afterward, the patient experienced prolonged apnea. The injection of propofol was interrupted and she rapidly returned to her previous state without resuscitation. The patient woke up 13 minutes after we stopped injecting propofol with no consequence on her health.

Discussion

This study shows that transitory sedation using propofol for terminally ill patients hospitalized in a palliative care unit can offer optimal comfort during painful care procedures.

It is sometimes necessary to reduce the patient's awareness during certain procedures despite the current options we have for analgesics and anxiolytics. Indeed, during care procedures, uncovering wounds and bare bodies can cause discomfort, in addition to actual physical nociceptive and neuropathic pain: anxiety, fear, disturbance of body image, idea of impossible recovery and death, feeling of dependence, and so on. The procedure we recommend could help reduce patients' fear of uncomfortable care procedures. The medical staff can deliver qualitative care without feeling like they are causing discomfort. The patient thus feels relieved to be clean and to have less painful and malodorous wounds.

Midazolam is currently the most highly recommended sedative for short procedural sedation at the end of life.^8,9 It presents interesting properties: IV infusion, relatively short duration of action and half-life, and amnesic effect. Our study suggests that propofol is even better. We show that the average duration of induction is 4 minutes, and that despite a deep sedation allowing comfortable care procedures, our patients woke up within an average of 11.5 minutes. There are four advantages to this: respiratory risk is lower; the patient can rapidly enjoy his or her relational life after care procedures; in case of an incident, the sedative effect quickly fades away and the patient retrieves his or her respiratory capacity; the medical staff can promptly attend to other tasks. The main disadvantage of propofol is the need for an IV access.

The respiratory and cardiovascular depressant effects of propofol depend on the administered dose. We showed that small doses are sufficient to sedate a patient at the end of life and lead to few complications. Only one case of transient respiratory side effects was observed. Because it was well tolerated, we do not specifically recommend that an anesthesiologist be present. However, we advise doctors who administer procedural sedation to be familiar with first aid techniques such as airway management. Administering an oxygen therapy during procedures can prevent the harmful consequences of a potential prolonged apnea. An aspiration device should be available to prevent the consequences of potential regurgitations.

The patient who had the longest wake-up time (18 minutes) had been given an injection of fentanyl immediately before the procedure. As a precaution, the patient was administered naloxone. We advise against any injection of opioids right before sedation to avoid respiratory risk and prolonged wake-up phases.

Conclusions

When administered after our procedure, propofol can provide better comfort to patients during painful care procedures at the end of life. The patients wake up quickly. Further studies will verify these initial results and ensure there are no major drawbacks. Propofol and midazolam should also be directly compared in terms of efficiency and safety.

Footnotes

Acknowledgments

This work was supported by the Pallia-Aide Association and the Centre Hospitalier Universitaire de Nice. This study was financed by the 2012 research grant “Douleur du Cancer” of the Archimedes Pharma France laboratories. The study sponsor had no influence on the study design, data collection, analysis, data interpretation, or decision to submit the article for publication.

Author Disclosure Statement

No competing financial interests exist.

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