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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094On-line version ISSN 1806-907X

Rev. Bras. Anestesiol. vol.56 no.5 Campinas Sept./Oct. 2006 



Comparative study of midazolam with ketamine S(+) versus midazolam with uterine paracervical block for manual intrauterine aspiration*


Estudio comparativo de midazolam con cetamina S(+) versus midazolam con bloqueo paracervical uterino para aspiración manual intrauterina



Vonaldo Torres de Almeida, M.D.I; Aurélio Molina, M.D.II

IAnestesiologista do CISAM/UPE; Mestrando em Tocoginecologia na UPE; Anestesiologista da Secretaria de Saúde de Pernambuco
IIProfessor Doutor do Departamento de Tocoginecologia da FCM/UPE; Coordenador do Mestrado em Tocoginecologia da FCM/UPE

Correspondence to




BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the efficacy, postoperative analgesia, the degree of satisfaction of the patients submitted to manual intrauterine aspiration, and whether the patient would recommend the technique, by comparing two anesthetic techniques.
METHODS: A prospective study was done with 80 patients divided, randomized, in two groups. All of them received IV midazolam. Afterwards, the MC Group received IV Ketamaine S(+) and the MP Group underwent paracervical uterine block. In the operating room, the efficacy of the technique was evaluated by 3 observers (the researcher, the obstetrician, and the obstetrics resident) and, after one hour, an observer, who did not know which technique had been used, evaluated the postoperative analgesia, and the degree of satisfaction and whether or not the patient would recommend the technique, using a verbal scale.
RESULTS: The techniques were effective in 95% of the patients in the MC group and 76.7% of the patients in the MP group (p = 0.04). Among the patients in the MC group, 67% did not experience pain after 1 hour, while in the MP group the percentage of pain free patients was 33.3% (p < 0.01, and a relative risk = 2). Both groups had a 90% satisfaction rate and 90% would recommend the technique.
CONCLUSIONS: We concluded that anesthesia with midazolam and ketamine S(+) was better than the association of midazolam with uterine paracervical block for manual intrauterine aspiration, regarding both efficacy and postoperative analgesia. The index of satisfaction was very high for both techniques.

Key Words: ANALGESICS: ketamine; ANESTHETIC TECHNIQUES, Regional: uterine paracervical block; HYPNOTICS, Benzodiazepines: midazolam; SURGERY, Gynecologic: manual intrauterine aspiration.


JUSTIFICATIVA Y OBJETIVOS: Evaluar la efectividad, la analgesia postoperatoria y el grado de satisfacción y recomendación de las pacientes sometidas a la aspiración manual intrauterina a través de la comparación de las técnicas anestésicas.
MÉTODO: Formando parte de un estudio de prospección, se estudiaron 80 pacientes distribuidas aleatoriamente en 2 grupos. Todas recibieron midazolam por vía venosa. En seguida, el Grupo MC, recibió cetamina S(+) por vía venosa y el Grupo MP bloqueo paracervical uterino. En la sala de cirugía la eficacia de la técnica fue evaluada por tres observadores (el investigador, el obstetra y el residente de obstetricia) y después de una hora, fue evaluada por un observador que desconocía la técnica realizada, la analgesia postoperatoria y los grados de satisfacción de recomendación de la paciente mediante escala verbal.
RESULTADOS: Las técnicas se mostraron eficientes en 95% de las pacientes del Grupo MC y 76,7% de las pacientes del grupo MP (p = 0,04). Entre las pacientes del Grupo MC, 67 % no presentaron dolor después de una hora, mientras que en el grupo MP el porcentaje de pacientes sin dolor fue de un 33,3% (p < 0,01 y un riesgo relativo = 2). Ambos grupos tuvieron un 90% de satisfacción y de recomendación de la técnica.
CONCLUSIONES: En ese estudio se concluyó que la anestesia con midazolam y cetamina S(+) fue superior a la asociación de midazolam con bloqueo paracervical uterino para aspiración manual intrauterina, tanto con relación a la eficacia como a la analgesia postoperatoria, bajo el punto de vista de los observadores. En la opinión de las pacientes el índice de satisfacción fue alto con las dos técnicas.




Spontaneous abortion in the first trimester is the most common obstetric intercurrence (more than 10% of pregnancies). Since the mid XX Century, manual intrauterine aspiration is considered the gold standard for emptying the uterus following spontaneous abortion, which, in most cases, is performed under general anesthesia 1. Manual intrauterine aspiration is also considered a standard surgical procedure for early interruption of pregnancy in countries where this procedure is legal 2.

Patients can experience two types of pain with manual intrauterine aspiration. Severe visceral pain that occurs during dilation of the cervix, as well as with the stimulation of the internal cervical ostium, which is transmitted by the dense network of nerves that surround the cervix, and the diffuse, colic pain caused by moving the uterus, curettage of the uterine wall, and muscle spasm secondary to emptying the uterine cavity. Uterine pain is transmitted from the fundus through the uterine nerves that follow the uterosacral and utero-ovarian ligaments. The hypogastric plexus innervates the body and fundus of the uterus, while the uterovaginal plexus innervates the cervix and upper portion of the vagina 3. The main reason for associating midazolam and ketamine is the rapid onset of analgesia of ketamine 4, while its side effects are decreased by midazolam 5.

The use of ketamine (S+), the levorotatory component of the original racemic mixture is twice or three times more potent than the dextrorotatory, R component, reduces the dose of the anesthetic, while providing for a faster postoperative recovery 6. Consequently, ketamine S(+) shows greater analgesic and hypnotic actions with lower psychoactive and circulatory effects when compared to the racemic mixture 7.

The administration of ketamine should be preceded by sedating doses of midazolam in order to prevent or reduce adverse reactions in the immediate postoperative period 8.

The efficacy of the paracervical uterine block in relieving pain has been established in a placebo-controlled study 9 of patients submitted to manual intrauterine aspiration for the treatment of incomplete abortion. Its association with midazolam is aimed at improving patient satisfaction with this technique of uterine emptying. The goal of pain control is to minimize patient discomfort and anxiety, with the lowest possible risk.

The objective of this study was to identify which of the two techniques is closer to the binomial comfort-risk.



The study was approved by the Ethics Committee of the Maternity (Centro Integrado de Saúde Amaury Medeiros). Patients signed an informed consent. Eighty patients, 18 years or older, physical status ASA I, with up to 12-week gestation, submitted to manual intrauterine aspiration for incomplete or retained abortion, participated in this randomized, partially blind study. Patients with infected abortion or with psychiatric conditions were excluded. Sample size was determined based on the study of Donati et al. 10.

Patients were divided in two equal groups: MC Group – 40 patients who received IV midazolam (0.1 and ketamine S(+) (1.5; and MP Group – 40 patients who received IV midazolam (0.1 and paracervical uterine block with 1% lidocaine without vasoconstrictor. Anesthesia was performed by the injection of 2 mL of the local anesthetic in the transition between the smooth cervical epithelium and the vaginal tissue, 2 to 3 mm deep, at the points corresponding to 1, 3, 5, 7, 9, and 11 hours 3.

Patients were monitored as usual, i.e., with ECG, SpO2, and noninvasive blood pressure. In the operating room, venous cannulation was performed with a peripheral 20G catheter. Both groups received midazolam, and after waiting two minutes for its effect on brain electrical activity 11, the patient was placed in the lithotomy position and ketamine S(+) was administered or the uterine paracervical block was performed. After the anesthesia was performed, there was a four-minute waiting period, taking into consideration latency times. All patients received oxygen by face mask (8 L.min-1).

The technique deemed efficient was the one that provided adequate conditions to realize the proposed procedure. It was considered flawed when it did not immobilize the patient adequately, when it presented severe side effects (hypertension, tachydysrhythmia), or when the patient grimed in pain. These variables were evaluated by the researcher, obstetrician, and resident aiming at reducing researcher bias regarding the results of the anesthesia. In case midazolam and ketamine S(+) were not efficient, fentanyl would be added; if it happened with midazolam associated with uterine paracervical block, ketamine S(+) would be added. Postoperative analgesia, degree of patient satisfaction, and whether the patient would recommend it were evaluated by an observer unaware of the type of anesthesia used one hour after the procedure was completed. The evaluation of pain intensity was done using a verbal scale of five terms 12, a version of the McGill Pain Questionnaire Scale 11, after the patient informed her name, age, address, and where she was. The terms used were: absent (1), mild (2), moderate (3), severe (4), and very severe (5) 12,13. The degree of satisfaction was determined using a verbal scale composed of the following statements: very pleased, pleased, not so pleased, unsatisfied, and extremely unsatisfied 14. Whether the patient would recommend it or not was determined using the following statements: would repeat it or not in a future, similar event. The duration of the surgery was expressed in full minutes, counted from the introduction of the speculum.

Initially, a bivaried statistical analysis to verify the randomized distribution was performed. Afterwards, an analysis was done to verify the associations among the dependent variable (type of anesthesia) and the independent variables (effects). A few numerical variables were categorized, according to their distribution, in order to be analyzed; the cutting points were determined according to the median or mean, as in the case of the duration of the surgery, and length of time for total recovery and the patient's discharge. Some continuous variables were grouped in classes for statistical analysis.

In every step of the analysis, an alpha error was considered significant if smaller than 5% and a confidence interval of 80%.

Patients who were allocated for the study but whose manual intrauterine aspiration was converted into conventional curettage, needed an exploratory laparotomy, or the anesthetic technique failed, were analyzed in their original group (intention of treatment analysis). Contingency tables, of the 2 x 2 type, were done for the categorical variables using the Chi-square test for associations. A p smaller than 0.05 was considered significant.



Variables such as age, number of pregnancies, weight, gestational age, duration of the surgery, and preoperative fasting, that could be confounding factors, were equally distributed in both groups. The difference was non-statistically significant (Table I).



Among patients who received the association of midazolam and ketamine S(+), the technique was efficient in 95% of the cases (38 patients) against 76.7% (32 patients) of the patients who were sedated with midazolam and underwent paracervical uterine block. The probability for the patient who underwent manual intrauterine aspiration with midazolam and ketamine S(+) to have a successful procedure was 19% higher than the group who received midazolam and underwent paracervical uterine block (RR of 1.19), with a statistically significant difference value of Chi-square = 4.06 and p < 0.04 (Table II).



Pain intensity evaluated in the postoperative period showed a statistically significant difference between both groups (Table III).



The categories of pain for analysis were: absent, mild, moderate, severe, and very severe, were divided in two categories: absence of pain and presence of pain (mild, moderate, and severe). Very severe pain was not recorded. It demonstrated that 66.7% of the patients in the MC group did not experience pain one hour after the procedure, and that they were more likely (2:1) to experience no pain in the postoperative period than the patients in the MP group (Table IV).



The degree of satisfaction was composed of two aspects. Besides asking the patient whether she was pleased with the anesthetic technique, she was also asked whether she would repeat the same technique in the future if a similar procedure were required (Tables V, VI, and VII). The difference between both groups was non-statistically significant. To be analyzed, satisfaction was divided in: pleased (very pleased and pleased), unsatisfied (not so pleased, unsatisfied, and very unsatisfied), and did not know/did not want to answer.







The length of time (duration of the surgery) necessary to perform the manual intrauterine aspiration was different between the MC group (12.37 ± 4.45) and the MP group (17.52 ± 5.31). The duration of the procedure was shorter in the patients who underwent general anesthesia, and this difference was statistically significant. X2 = 19.46, gL = 1, and p < 0.01.

In the MP group the procedure lasted longer and the patients experienced more pain in the postoperative period. To discard the possibility that the patients in the MP group experienced more pain because the procedure lasted longer, we selected only the patients who experienced pain in the postoperative period in order to identify any differences among them. We used the mean of the procedures, i.e., 15 minutes as the cutting point (Table VIII).




We did not find in the literature any studies focusing on the association of midazolam with ketamine S(+) or midazolam with uterine paracervical block for manual intrauterine aspiration, which is a painful procedure if performed without any type of analgesia 15. These associations are justified since midazolam and ketamine were used in short duration procedures 16, benzodiazepines reduce the psychomimetic effects of ketamine 17, and ketamine has specific analgesic effects on visceral pain 18. The levorotatory form (ketamine S+) was used because it has a short elimination half-life, of 2 to 3 hours 19,20, it is 2 to 3 times more potent than the dextrorotatory isomer (ketamine R-) in relieving pain, and, in equianalgesic doses, it produces less psychological alterations than the racemic and dextrorotatory forms 21,22.

The double-blind technique is useful when similar treatments are compared 23. In this study two anesthetic techniques using different administration routes were used: one is completely intravenous and the other uses intravenous sedation associated with paracervical uterine block with a local anesthetic. Therefore, it was impossible to "mask" the type of anesthetic procedure used. The anesthetic techniques used for manual intrauterine aspiration were efficient in both groups; however, general anesthesia was considered more effective than sedation associated with paracervical uterine block. In an attempt to decrease the researcher's interference in the evaluation of this variable, the evaluations by the obstetrician and the resident were associated. The interference of the researcher was decreased even further when the efficiency of the technique was associated with patient satisfaction. The study demonstrated a high efficiency index, patient satisfaction, and a desire to use the technique again in a future event. It is unlikely that a patient submitted to an inefficient technique resulting in intraoperative or postoperative pain and undesirable side effects would be satisfied and willing to be submitted to the same type of anesthesia in the future. We should emphasize that the last data were collected by an observer who did not know which technique was used. These efficiency data agree with that of others who used midazolam and ketamine 24-26.

After one hour, pain was less severe in the MC group. This can be explained by the pharmacological action of ketamine S(+), including its effects on opioid receptors 27,28. Pain severity – mild and moderate – in patients who underwent paracervical uterine block was high, i.e., 60% of the cases (37.5% of mild pain and 22.5% of moderate pain), probably due to the inefficiency of the method in blocking the transmission of all painful stimuli generated during uterine emptying. The association of painkillers or anti-inflammatories with paracervical uterine block would enable improvement of postoperative analgesia in this group of patients. The severity of postoperative pain also depends on the duration of the surgery 29. Pain was more severe and the procedure lasted longer in the MP group; it was due not only to the latency of the paracervical block (4 minutes), but also because patients were less relaxed during the procedure. For patients in the MP group, the difference among patients who experienced postoperative pain whose procedure lasted more than 15 minutes or less than 15 minutes was non-statistically significant. As for the MC group, there was no statistically significant difference between postoperative pain severity and duration of the procedure.

In both groups, around 90% of the patients were not only pleased, but would also use the same anesthetic technique in the future if needed. Despite 62.5% of the patients in the MP group reported mild pain, they also reported the same satisfaction.

In this study, anesthesia with midazolam and ketamine S(+) was higher than midazolam associated with uterine paracervical block for manual intrauterine aspiration, both in intraoperative efficiency and postoperative analgesia. The patient satisfaction index was high for both techniques.



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Correspondence to:
Dr. Vonaldo Torres de Almeida
Rua Mamanguape 518/701
Boa Viagem
51020-250 Recife, PE

Submitted for publication 03 de novembro de 2005
Accepted for publication 23 de junho de 2006



* Received from Centro Integrado de Saúde Amaury de Medeiros da Universidade de Pernambuco (CISAM/ UPE), Recife, PE

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