Sedation-analgesia in elective colonoscopy: propofol-fentanyl versus propofol-alfentanil

Abstracts

JUSTIFICATIVA E OBJETIVO: Sedação e analgesia são recomendadas em colonoscopia para propiciar conforto, pois são procedimentos invasivos e podem ser dolorosos. Este estudo teve como objetivo comparar as combinações de propofol-alfentanil e propofol-fentanil para sedação e analgesia em pacientes submetidos à colonoscopia eletiva. MÉTODOS: Estudo prospectivo e randomizado. Participaram do estudo 80 pacientes, ASA I-II, entre 18 e 65 anos. A indução de sedação e a analgesia foram feitas com propofol (1 mg.kg-1) e fentanil (1 µg.kg-1) no grupo propofol-fentanil (PF) e com propofol (1 mg.kg-1) e alfentanil (10 µg.kg-1) no grupo propofol-alfentanil (PA). Para manutenção, doses adicionais de propofol foram administradas em bolus de 0,5 mg.kg-1 para obter escores de 3-4 na Escala de Sedação de Ramsey (ESR). Registrados os dados demográficos, a frequência cardíaca, a pressão arterial média (PAM), a saturação de oxigênio da hemoglobina (SpO2), os valores da ESR, o tempo de colonoscopia, a dose total de propofol, as complicações, o tempo de recuperação e o tempo para alta, bem como os escores de satisfação do colonoscopista e do paciente. RESULTADOS: A PAM aos 15 minutos no Grupo PA foi significativamente maior do que no Grupo PF (p = 0,037). A frequência cardíaca média do grupo PA foi maior no início do que nas mensurações subsequentes (p = 0,012, p = 0,002). A média da dose total de propofol do Grupo PA foi significativamente maior do que a do Grupo PF (p = 0,028). O tempo médio de recuperação do grupo PA foi significativamente maior do que o do grupo PF (p = 0,032). CONCLUSÃO: Fentanil proporciona melhores condições de operação e reduz a necessidade de doses adicionais de propofol. Essas vantagens diminuem o tempo de recuperação. Portanto, propofol-fentanil é superior ao propofol-alfentanil para sedação e analgesia em colonoscopia.

ANALGÉSICOS, Opióides, fentanil, alfentanil; ANESTÉSICOS, Venoso, propofol; CIRURGIA, Endoscopia; Colonoscopia

JUSTIFICATIVA Y OBJETIVO: La sedación y la analgesia están recomendadas en la colonoscopia para propiciar la comodidad, porque son procedimientos invasivos y pueden ser dolorosos. Este estudio tuvo el objetivo de comparar las combinaciones de propofol-alfentanilo y propofol-fentanilo para la sedación y la analgesia en pacientes sometidos a la colonoscopia electiva. MÉTODOS: Estudio prospectivo y aleatorio. Participaron en el estudio 80 pacientes, ASA I-II, entre 18 y 65 años. La inducción de sedación y la analgesia fue hecha con propofol (1 mg.kg-1) y fentanilo (1 µg.kg-1) en el grupo propofol-fentanilo (PF) y con propofol (1 mg.kg-1) y alfentanilo (10 µg.kg-1) en el grupo propofol-alfentanilo (PA). Para el mantenimiento, dosis adicionales de propofol se administraron en bolos de 0,5 mg.kg-1 para obtener las puntuaciones de 3-4 en la Escala de Sedación de Ramsey (ESR). Se registraron los datos demográficos, la frecuencia cardíaca, la presión arterial promedio (PAP), la saturación de oxígeno de la hemoglobina (SpO2), los valores de la ESR, el tiempo de colonoscopia, la dosis total de propofol, las complicaciones, el tiempo de recuperación y el tiempo para el alta, como también las puntuaciones de satisfacción del colonoscopista y del paciente. RESULTADOS: La PAP a los 15 minutos en el Grupo PA fue significativamente mayor que en el Grupo PF (p = 0,037). La frecuencia cardíaca promedio del grupo PA fue mayor al inicio que en las mensuraciones posteriores (p = 0,012, p = 0,002). El promedio de la dosis total de propofol del Grupo PA fue significativamente mayor que la del Grupo PF (p = 0,028). El tiempo promedio de recuperación del grupo PA fue significativamente mayor que el del grupo PF (p = 0,032). CONCLUSIONES: El Fentanilo proporciona mejores condiciones de operación y reduce la necesidad de dosis adicionales de propofol. Esas ventajas reducen el tiempo de recuperación. Por tanto, el propofol-fentanilo es superior al propofol-alfentanilo para la sedación y la analgesia en la colonoscopia.

CIRUGÍA, Endoscopia; Colonoscopia; ANESTÉSICOS, Intravenoso, propofol; ANALGÉSICOS, Opioides, fentanil, alfentanil

SCIENTIFIC ARTICLE

^IŞişli Etfal Training and Research Hospital, Department of Anesthesiology and Intensive Care Medicine, Istanbul, Turkey

^IIŞişli Etfal Training and Research Hospital, Department of General Surgery, Istanbul, Turkey

Corresponding author

ABSTRACT

BACKGROUND AND OBJECTIVES: Sedation-analgesia is recommended for comfortable colonoscopy procedures, which are invasive and can be painful. This study aimed to compare the combinations of propofol-alfentanil and propofol-fentanyl for sedation-analgesia in elective colonoscopy patients.

METHODS: This prospective and randomized study was planned in ASA I-II groups and included 80 patients between the ages of 18 and 65 years. Sedation-analgesia induction was performed as 1 µg.kg^-1 fentanyl, 1 mg.kg^-1 propofol in the propofol-fentanyl group (Group PF) and 10 µg.kg^-1 alfentanil, 1 mg.kg^-1 propofol in the propofol-alfentanil group (Group PA). Patients' scores were limited to 3-4 values on the Ramsey Sedation Scale (RSS) by 0.5 mg.kg^-1 bolus additional doses of propofol in sedation-analgesia maintenance. We recorded demographical data, heart rate, mean arterial pressure (MAP), oxygen saturation of hemoglobin (SpO2), RSS value, colonoscopy time, total dose of propofol, complications, recovery time, and discharge time, as well as colonoscopist and patient satisfaction scores.

RESULTS: MAP at the 15^th minute in Group PA was significantly higher than in Group PF (p = 0.037). Group PA's beginning mean heart rate was higher than the mean heart rate at subsequent readings (p = 0.012, p = 0.002). The mean total propofol dose of Group PA was significantly higher than the total dose of Group PF (p = 0.028). The mean recovery time of Group PA was significantly longer than that of Group PF (p = 0.032).

CONCLUSION: Fentanyl provides better operative conditions and reduces the need for additional propofol doses. These advantages cause a shorter recovery time. Therefore, propofol-fentanyl is superior to the propofol-alfentanil for sedation-analgesia in colonoscopy.

Keywords: Alfentanil; Colonoscopy; Fentanyl; Propofol.

Introduction

Due to the frequency of colorectal malignancies in industrial countries, diagnostic and therapeutic colonoscopy rates have increased dramatically. Colonoscopy-induced pain and anxiety affects both patient and colonoscopist comfort¹. The best sedation/analgesia type for gastrointestinal endoscopic procedures is still not clear². Although some studies recommend that the colonoscopy procedure can be performed without sedation, various other studies have reported this is not possible and that sedation administration before the procedure is safer for both patient and colonoscopist^3-5. Both anesthesia and sedation-analgesia are options for colonoscopy procedures⁶, but conscious sedation is recommended¹. Conscious sedation allows the patient to give responses to verbal or tactile stimulation and provides the attendance of respiratory and cardiovascular functions¹.

Doctors performing colonoscopy screenings throughout the world tend to prefer sedation-analgesia. Midazolam, propofol and/or alfentanil or pethidine combinations, α-agonists, and neuroleptics are used for sedation-analgesia^6,7.

This study aimed to compare the hemodynamic effects, recovery and discharge times, patient-colonoscopist satisfaction, and complications of propofol-fentanyl and propofol-alfentanil combinations in elective colonoscopy procedures.

Material and methods

After obtaining the Ethics Committee's approval and the patients' written informed consents, this prospective and randomized 80-patient study proceeded in Şişli Etfal Training and Research Hospital, Istanbul, Turkey. The research team selected a group of ASA I-II patients between 18 and 65 years scheduled for elective colonoscopy screening. Researchers verified the status of patients' 8-hour fasting period and the absence of alcohol or sedative drug use 24 hours before the colonoscopy procedure. The same anesthesiologist administered sedation-analgesia on all patients. The exclusion criterions of this study were pregnancy, gastrointestinal hemorrhage, known or predicted airway difficulty, alcohol or drug addiction, neuropsychiatric disease, severe heart or respiratory insufficiency, and sedative drug allergy.

An independent nurse performed randomization by sequentially opening numbered opaque envelopes with group allocation cards in a random computer generated sequence. Patients were not informed of the group in which they were included.

We explained the oral scoring system to the patients, which is on a scale of 1 to 10 and necessary to evaluate the patient satisfaction. After patients were admitted to the gastrointestinal endoscopy unit, intravenous (IV) catheterization was performed with 18-gauge IV catheters and a 0.9% NaCl infusion was started; patients received no premedication. The lateral positioned patients were monitored with noninvasive systemic mean arterial pressure (MAP), 3-channel ECGs, and pulse oximetry (SpO₂). Patients received 3L.min^-1 oxygen by nasal catheter.

The research team performed sedation-analgesia induction as 1 µg.kg^-1 fentanyl and 1 mg.kg^-1 propofol in Group PF and 10 µg.kg^-1 alfentanil and 1 mg.kg^-1 propofol in Group PA. After the beginning of the colonoscopy screening, the patients' scores were limited to 3-4 values on the Ramsey Sedation Scale (RSS) (Table 1) by 0.5 mg.kg^-1 bolus additional doses of propofol in sedation-analgesia maintenance. We recorded heart rate, MAP, SpO₂, and RSS values before the procedure, at the beginning of the colonoscopy screening, and at 5-minute intervals during the procedure.

We established colonoscopy time as the time from induction to the end of the colonoscopy screening. The recovery time was the time from induction until the RSS scores progressed to value 2. We recorded total propofol doses and complications. After the procedure, patients with scores of 9 or greater, according to the Aldrete Score (Table 2), were discharged. After recovery, patients orally scored satisfaction on a scale of 1 to 10 (1: not satisfied, 10: very satisfied). Colonoscopist satisfaction was scored with 10 cm visual analog scale. We recorded colonoscopist and patient satisfaction scores.

We recorded anesthesia and endoscopy-related complications that appeared during or after procedure, such as allergic reactions, bradycardia, tachycardia, hypotension, hypertension, respiratory depression, desaturation, perforation, bleeding, nausea and vomiting. Desaturation was defined as the decrease of oxygen saturation to below 85%.

We calculated the sample sizes with the assumption of at least 30% possible difference in our study between any two groups. Therefore, we allocated 40 patients into each group to obtain an alpha error of 5% and statistical power of 80%.

For data evaluation and descriptive statistics (mean, standard deviation), researchers used paired variance analysis for repeated measures of the groups and the Newman-Keuls multiple comparison test for subgroups. We used an independent t-test for comparisons between the two groups and the chi-square test for comparison of qualitative parameters. Results were considered statistically significant when the p value was under 0.05.

Results

Age, sex, weight, ASA values, colonoscopy times, and complication rates were similar in both groups (Table 3). Complications were apparent in 21 patients. Although there was no respiratory depression, 8 patients from Group PF, and 12 from Group PA experienced desaturation. These patients did not need endotracheal intubation or mask ventilation; vocal or tactile stimuli produced adequate recovery from desaturation. Only one patient had nausea and vomiting; this patient was in Group PA. All of the patients that experienced complications were discharged safely. We did not see endoscopy-related complications.

The MAP mean at the 15^th minute in Group PA was significantly higher than in Group PF (p = 0.037), but there were no differences between the two groups at all other times of MAP (Table 4). Similar to Group PA, Group PF showed no significant differences when the beginning MAP mean was compared with the mean at all other times.

There was no difference in mean heart rate between the two groups at any time. Although mean heart rates were similar in Group PF for all recording times, significant differences were found in Group PA (p = 0.0001). Group PA's beginning mean heart rate was significantly higher than the mean heart rates for all other recording times (p = 0.002, p = 0.012), which were similar to each other (Table 5). There were no significant differences between the two groups in mean oxygen saturation values (Figure 1).

Mean RSS values were similar when comparing the groups. Group PF's mean RSS values differed significantly for recording times (p = 0.0001). Group PF's first and 5^th minute mean RSS values were significantly higher than at other times (p = 0.002, p = 0.045) when no differences were noted. Group PA's mean RSS values had significant differences during all the recording times (p = 0.017). Group PA's first-minute mean RSS value was significantly higher than the 15^th, 20^th, 25^th, and 30^th minute values (p = 0.002, p = 0.022) (Table 6).

The mean total propofol dose of Group PA was significantly higher than Group PF (p = 0.028) and the mean recovery time of Group PA was significantly longer than the recovery time of Group PF (p = 0.032). Mean discharge times and colonoscopist and patient satisfaction scores were similar in both of the groups (Table 7).

Discussion

Propofol is a short-acting, intravenous hypnotic, which provides rapid and complete recovery from anesthesia. When propofol is used as the sole anesthetic agent for an invasive procedure, very high doses (14.9 mg.kg^-1.h^-1) are required for toleration of the procedure². Both direct myocardial depression and peripheral vasodilation are propofol's cardiovascular depressant effects, which are dose and concentration dependent^7,8. Complications, such as hypotension, respiratory depression, and decreased upper airway protective reflex activity can appear with the use of high-dose propofol⁷. Because the propofol is insufficient for analgesia, combining propofol with an intravenous opioid is recommended to increase the quality of sedation^7,9.

Both alfentanil and fentanyl can be used safely in colonoscopy procedures. Fentanyl clinical potency is 3-10 times that of alfentanil. Alfentanil, a tetrazole derivative of fentanyl, crosses rapidly to highly perfused tissues like those of the brain, then distributes to the peripheral tissues. Both alfentanil and fentanyl cross the blood brain barrier rapidly. Alfentanil has rapid onset and produces unconsciousness 50 seconds after administration. Respiratory depression and unconsciousness occur at the same time with alfentanil; however, unconsciousness occurs 30-60 seconds after respiratory depression in fentanyl because fentanyl has higher lipid solubility than alfentanil and fentanyl's plasma concentration accumulates in tissue compartments before the onset of sufficient opioid effects. Less accumulation of alfentanil provides greater binding of plasma concentrations to opioid receptors and a more rapid onset of effects^8,10.

Because the propofol and alfentanil have rapid onset and are short acting, they are useful for sedation-analgesia¹¹ and the propofol-alfentanil combination is successful in analgesia⁹. Avramov et al. reported that the propofol-combined opioid provides analgesia and amnesia, as well as reduces incidences of nausea, vomiting, and respiratory depression¹². In the current study, only one patient had nausea and vomiting; this patient was in Group PA.

Despite the appropriate sedation level achieved in opioid use, colonoscopy patients experienced decreased upper airway protective reflex activity and upper airway management problems⁷. Alfentanil, as a short-acting opioid, was recommended for short procedures but when used as a sole agent, reports indicate that intraoperative and postoperative respiratory depression occurred more frequently^12,13. In the current study, the incidence of respiratory complications was higher in Group PA than in Group PF. Although there was no respiratory depression, 8 patients from Group PF and 12 from Group PA experienced desaturation. These patients did not need endotracheal intubation or mask ventilation; vocal or tactile stimuli produced adequate recovery from desaturation.

Roseveare et al. suggested that the propofol-alfentanil combination was more short-acting and effective than benzodiazepines were in colonoscopy screening¹⁴. Külling et al. compared the propofol-alfentanil combination with midazolam and meperidine. They reported that the propofol-alfentanil combination resulted in more rapid recovery and increased patient satisfaction in colonoscopy¹⁵.

In one study of midazolam combinations, researchers compared meperidine, alfentanil, fentanyl, and sufentanil combinations in gastroscopy. Recovery times were reportedly shorter in the sufentanil and alfentanil groups¹⁶. In Holloway et al.'s study, midazolam combined with alfentanil and fentanyl were compared in colonoscopy. They reported that although alfentanil and fentanyl had similar recovery times, alfentanil provided better operative conditions¹⁷. The current study compared propofol combined with fentanyl and alfentanil but the results did not confirm the previous studies. Recovery time was shorter and the mean propofol dose was less in Group PF than in Group PA.

The mean colonoscopy times were 20, 68 ± 10, 2 minutes in Group PA and 17, 5 ± 7, 39 minutes in Group PF. Because alfentanil acting time is shorter than the colonoscopy time, additional propofol doses were needed, and the 15^th minute MAP values were higher in Group PA than in Group PF. Group PA's beginning mean heart rate was higher than at subsequent recording times, which researchers related to the additional doses of propofol. None of our patients had hypotension or bradycardia.

In our study, we used RSS for the evaluation of sedation level. Mean RSS values were similar in both of the groups. Bispectral Index (BIS) could be used to regulate the appropriate sedation level and to reduce the dosage of sedatives during endoscopy. There are studies that compare the use of RSS and BIS^18-20. One of these studies reported that the BIS was the method recommended for monitoring patients under sedation and BIS monitoring could prevent oversedation and related complications¹⁸. In this study, we consider RSS insufficient to evaluate oversedation¹⁸. Not using BIS monitoring could be considered the negative side of our study. Nonetheless, there are studies comparing RSS and BIS that reported evaluations of sedation levels and the dosage of sedatives used were similar^19,20. Since our country is a developing one, acquiring BIS monitor and electrodes is hard and expensive. In similar studies from our country, RSS was used for the evaluation of sedation level²¹.

A most significant finding is that the patient/colonoscopist satisfaction scores were similar and high in both of the groups. This emphasizes that sedation-analgesia is the golden key for a comfortable and safe colonoscopy experience.

Because fentanyl has a longer acting time than alfentanil, fentanyl provides better operative conditions and reduces the need for an additional propofol dose, which results in a shorter recovery time. The propofol-fentanyl combination is superior to the propofol-alfentanil combination for sedation-analgesia in colonoscopy procedures.

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Sedation-analgesia in elective colonoscopy: propofol-fentanyl versus propofol-alfentanil

Hacer Şebnem Türk^I; Meltem Aydoğmuş^I; Oya Ünsal^I; Hakan Mustafa Köksal^I,II; Mehmet Eren Açik^I; Sibel Oba^I

Publication Dates

• Publication in this collection
  22 July 2013
• Date of issue
  Aug 2013

History

• Received
  02 May 2012
• Accepted
  09 July 2012