Prevention of itching after spinal sufentanil: effects of droperidol, nalbuphine, ondansetron and the association of them

Abstracts

JUSTIFICATIVA E OBJETIVOS: O uso espinhal de opióides pode causar alguns efeitos indesejáveis, dentre os quais, o mais freqüente é o prurido que, apesar de sua baixa morbidade, pode proporcionar desconforto intenso ao paciente e prolongar o período de internação. O objetivo deste estudo foi avaliar diversas opções terapêuticas no tratamento profilático do prurido após administração de sufentanil por via subaracnóidea. MÉTODO: Foram distribuídos de maneira aleatória, por sorteio, 100 pacientes a serem submetidos à intervenção cirúrgica não-obstétricas em cinco grupos, de acordo com o tratamento utilizado: controle (ausência de tratamento - C); droperidol 2,5 mg (D); nalbufina 10 mg (N); associação dos medicamentos anteriores (DN) e ondansetron 8 mg (O). O prurido foi avaliado quantitativamente 30 minutos, 1, 2, e 3 horas após a administração subaracnóidea de sufentanil. RESULTADOS: Os grupos C e O apresentaram incidência significativamente maior de prurido em relação aos grupos D, N e DN. Entretanto, não houve diferença significativa na necessidade de tratamento específico com naloxona entre os grupos tratados. CONCLUSÕES: O tratamento profilático do prurido neste estudo, independentemente do fármaco utilizado, diminuiu sua intensidade e limitou a necessidade de tratamento específico com naloxona.

ANALGESIA; ANALGÉSICOS, Opióides; ANTAGONISTAS; ANTIEMÉTICOS; ANTIEMÉTICOS; COMPLICAÇÕES

SCIENTIFIC ARTICLE

Prevention of itching after spinal sufentanil: effects of droperidol, nalbuphine, ondansetron and the association of them^*

Profilaxis del prurito inducido por la administración subaracnoidea de sufentanil: influencia do droperidol, da nalbufina, do ondansetron y da combinacion de elles

André Kolm^I; Alexandre Alberto Fontana Ferraz, TSA^I; Norma Sueli Pinheiro Módolo, TSA^II; Fábio Ferrari, TSA^III; Eliana Marisa Ganem, TSA^II; Geraldo Rolim Rodrigues Júnior, TSA^III; Paulo do Nascimento Júnior, TSA^II; Giane Nakamura^IV; Lais Helena Camacho Navarro^IV; Rodrigo Moreira Lima^V

^IAnestesiologistas, Ex-Residentes do CET/SBA da FMB UNESP

^IIProfessores Adjuntos da FMB UNESP

^IIIProfessores Assistentes Doutores da FMB UNESP

^IVAnestesiologistas e Pós-Graduandas do Programa de Pós-Graduação da FMB UNESP

^VME₃ do CET/SBA da FMB UNESP

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Spinal opioids may cause some undesirable effects, the most frequent of which is itching. In spite of its low morbidity rate, itching may cause severe discomfort to patients in addition to prolonging hospital stay. This study aimed at evaluating different therapeutic options to prevent itching after spinal sufentanil.

METHODS: Participated in these study 100 patients scheduled for non-obstetric procedures, who were randomly distributed in five groups: control (no treatment - C); 2.5 mg droperidol (D); 10 mg nalbuphine (N); association of previous drugs (DN); and 8 mg ondansetron (O). Pruritus was quantitatively evaluated at 30 minutes, 1, 2 and 3 hours after spinal sufentanil.

RESULTS: Groups C and O had significantly higher incidence of itching as compared to groups D, N and DN. However, there has been no significant difference in the need for specific treatment with naloxone among groups.

CONCLUSIONS: Itching prevention in our study, regardless of the drug used, has decreased its severity and has limited the need for specific treatment with naloxone.

Key Words: ANALGESIA: spinal; ANALGESICS, Opioids: sufentanil; ANTAGONISTS: nalbuphine; ANTIEMETICS: droperidol, ondansetron; COMPLICATIONS: itching

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: El uso espinal de opioides puede ser causa de efectos indeseables, entre los que el prurito es el más frecuente y a pesar de su escasa morbilidad puede ser causa de intenso desconfort y prolongar el tiempo de internación. El objetivo de este estudio es evaluar diferentes opciones terapéuticas para la prevención del prurito que ocurre después de la administración subaracnoidea de sufentanil.

MÉTODO: Cien pacientes que iban a recibir cirugías no obstétricas fueron divididos aleatoriamente (sorteo) en 5 grupos de acuerdo al tratamiento preventivo usado: control (sin tratamiento, grupo C); droperidol 2,5 mg (grupo D); nalbufina 10 mg (grupo N); asociación de los medicamentos anteriores (grupo DN) y ondansetron 8 mg (grupo O). El prurito fue evaluado en forma cuantitativa 30 minutos, 1, 2 y 3 horas después de la administración subaracnoidea de sufentanil.

RESULTADOS: Los grupos C y O presentaron incidencia de prurito significativamente mayor comparados con los grupos D, N y DN. No obstante, no hubo diferencia entre los grupos en relación al uso de naloxona como tratamiento específico.

CONCLUSIONES: El tratamiento preventivo del prurito usado en este estudio, independiente del fármaco empleado, disminuyó la intensidad y limitó la necesidad de tratamiento con naloxona.

INTRODUCTION

Spinal opioids administration has increased in recent years, allowing effective and safe analgesia, in addition to improving local anesthetics action¹. However, some side effects have limited its use, among them itching, nausea, vomiting and urinary retention. These undesirable effects, although with low morbidity rate, bring discomfort to patients and may prolong hospital stay^2,3.

Sufentanil, highly liposoluble and potent µ receptor agonist, has been widely used due to the excellent improvement of local anesthetics administered to the neuraxis and to the low risk of late respiratory depression. However itching after sufentanil is common and sometimes severe⁴.

Different treatments have been proposed to prevent or treat this undesirable effect. Naloxone, opioid antagonist drug, would be the best choice. However its use has been associated to lower analgesia quality, in addition to undesirable cardiovascular effects in some cases^5,6.

Propofol has also been suggested as therapeutic option^7,8, but its effectiveness against itching is controversial⁹ and its cost is high. Another option would be droperidol, dopaminergic antagonist^10,11, which use has also been questioned¹².

Nalbuphine, k agonist - µ antagonist, has been used for this end and had its efficacy proven by different authors as therapeutic agent in spinal opioids-induced itching¹³.

More recently ondansetron, serotonin antagonist, is being successfully used to treat cholestasis and morphine-induced itching^14-17.

This study aimed at evaluating the efficacy of droperidol, of nalbuphine, of the association of both, and of ondansetron to prevent spinal sufentanil-induced itching.

METHODS

After the Human Research Ethics Committee, Hospital das Clínicas, Faculdade de Medicina, Botucatu approval, participated in this prospective randomized study 100 patients of both genders, aged 15 to 70 years, physical status ASA I and II, submitted to spinal anesthesia for non-obstetric procedures. Exclusion criteria were dermatologic diseases with itching, use of opioids 24 hours before surgery and when there was failure or patients refused the spinal anesthesia.

Patients were premedicated with oral diazepam (10 mg) one hour before procedure. Standardized monitoring for all patients consisted of pulse oximetry, cardioscope at D_II lead and noninvasive blood pressure. Lactated Ringer’s solution was infused after peripheral venous puncture, at the adequate rate to maintain hemodynamic stability.

Spinal puncture was performed with 25G Quincke needle in L₂-L₃ or L₃-L₄ interspace and, after CSF reflux, 15 mg hyperbaric bupivacaine and soon after 10 µg sufentanil were injected with separate syringes.

After sensory block installation, patients were randomly distributed in five groups: control (no treatment - C); 2.5 mg droperidol (D); 10 mg nalbuphine (N); 2.5 droperidol associated to 10 mg nalbuphine (DN); and 8 mg ondansetron (O). Drugs were administered before the onset of itching.

The following parameters were recorded at 30 minutes, 1, 2 and 3 hours after sufentanil injection: itching, sedation, nausea and vomiting. Parameters were quantitatively evaluated according to scales shown in table I.

Hypoxemia was defined as peripheral oxygen saturation below 90% and was corrected with 3 L oxygen per minute under facial mask. Hypotension (systolic blood pressure below 30% of baseline pressure) was treated with 5 to 10 mg of ephedrine. Intravenous 20 mg tenoxicam were administered to all patients for postoperative pain relief.

Statistical analysis was performed with the aid of the program Statview^® 5.2 (SPSS, Inc., San Raphael, CA, EUA). Kruskal-Wallis test was used to compare among groups. Sample size was calculated for a power of 80% (SigmaStat^® 2.03 - SPSS, Inc., San Raphael, CA, EUA) considering significant p < 0.05.

RESULTS

Groups were comparable in demographics, surgical procedure and physical status. There were no statistically significant differences among groups in hypotension, hypoxemia, nausea and vomiting. As to itching, there has been statistically significant difference between control and ondansetron groups as compared to remaining groups in the first and second hours, with lower incidence in groups treated with droperidol, nalbuphine and the association of both drugs (p < 0.05) (Figure 1).

Quantitative itching evaluation by the need for specific treatment with naloxone has shown lower intensity in treated groups as compared to control, regardless of the drug (p < 0.01) (Figure 2).

After drugs administration, sedation rate was lower for the control group and the ondansetron group in all studied moments (p < 0.05). In groups treated with droperidol or the association of droperidol and nalbuphine, all patients presented sedation of different intensities (Figure 1).

Naloxone was used in 40% of control group, 10% of droperidol group, 10% of nalbuphine group, 5% of droperidol/nalbuphine group and 5% of ondansetron group, showing that itching, regardless of its incidence, was less severe in treated groups as compared to control group.

DISCUSSION

Most common spinal opioids side effect is itching, although its severe presentation is only seen in 1% of patients¹⁸. Its action mechanism is still to be fully explained. Animal studies were the basis for the concept of an “itching center” located inferiorly in the spinal cord and indicating that the trigeminal nucleus would be involved in this mechanism¹⁹.

Itching may be generalized but is most common on face, neck and upper chest. On the face, it is more common on trigeminal-nerve innervated areas¹⁹, indicating cephalad CSF migration and interaction with the nucleus of this nerve, which in turn has opioid receptors also present on its nervous roots^20,21. This rostral movement of opioids toward baseline cisterns helps the access to the trigeminal nucleus⁹.

Some other mechanisms suggested for itching are based on histamine, tachycinine and interleukin release, substances which promote itching by themselves, but which have pro-inflammatory activity able to sensitize nervous terminations and lead to itching. In addition, 5-hydroxitriptamine (serotonin) may be an itching regulating substance by directly acting on its receptors, mechanism observed in cholestasis patients²².

In our study, the association of droperidol and nalbuphine was the most effective in decreasing itching after sufentanil administration, with 5% incidence at 30 minutes, 25% at one hour, 15% at two hours and 5% at three hours, although these results were not statistically different as compared to remaining groups. This effect was probably due to the fact that action mechanisms of these two drugs are different, thus contributing to the success of the treatment.

The droperidol group had 25% itching at 30 minutes, 35% at one hour, 30% at two hours and 30% at three hours. Horta et al.¹⁰ have shown the efficacy of 2.5 mg droperidol in decreasing itching alter spinal opioid. Doses higher than or equal to 5 mg have not increased the effectiveness of the treatment and mild sedation has not confirmed that this is the mechanism through which droperidol inhibits itching.

Droperidol is primarily bound to D2 dopaminergic receptors, but also acts on alpha₁ and alpha₂ adrenergic, 5HT-2 serotoninergic, H-1 histaminergic and µ opioid receptors¹¹. One cannot yet state that some of these receptors are involved with itching modulation by droperidol, although such fact has been shown by some studies^10,11.

The nalbuphine group had 30% itching at 30 minutes, 25% at one hour, 20% at two hours and 20% at three hours. Better results as compared to control group are probably due to its antagonist effect on µ receptors¹³.

The ondansetron group had itching incidence similar to control group in all studied moments. Itching severity in this group was comparable to other treatments based on the need for naloxone, however with the advantage of less sedation due to its action mechanism (selective 5-HT3 receptors inhibition)¹⁷.

REFERENCES

Submitted for publication July 6, 2005

Accepted for publication December 14, 2005

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*

Received from Departamento de Anestesiologia da Faculdade de Medicina de Botucatu, Universidade Estadual de São Paulo (FMB UNESP), Botucatu, SP

Publication Dates

• Publication in this collection
  22 Mar 2006
• Date of issue
  Feb 2006

History

• Accepted
  14 Dec 2005
• Received
  06 July 2005