Introduction

About 211 million pregnancies occur annually all over the world, of which, 46 million lead to abortion¹. Common abortion therapies include pharmaceutical and mechanical therapies.

Dilatation and curettage (D & C) is one of the mechanical methods used for abortion. In this operation, opening the cervix or dilatation is far more painful than curettage².The anesthetic method for this operation can be general (GA) or regional, GA is the most common anesthetic approach based on the surgeon and patients’ wish. Because bleeding is common in this operation, maintaining the hemodynamic during anesthesia is very important. The duration of the stay in the hospital is often short, and the patient can be discharged if they do not develop any complications³. So, it's best to use a method to get the patient to wake up and recover faster. Therefore, the choice type of drug in the general anesthesia should be carefully investigated and the best medicine be chosen⁴. Thiopental induces anesthesia by bonding to the position of ionophore chloride in the Gaba aminobutiric acid receptor (GABA) and inhibiting this receptor about 30 seconds after injection. It has no analgesic effect, but its effect on the cardiovascular system and the reduction of vascular resistance leads to hypotension and sometimes, reflex tachycardia⁵. Propofol is a drug with rapid onset and hepatic clearance after intravenous administration. It has direct antinociceptive effects but no analgesic effect. On the other hand, Ketamine acts on the NMDA via antagonistic effects, which increases the systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). Ketamine has dose-dependent effects of inaccuracy and analgesia⁶. Ketofol is a combination of two drugs (propofol and ketamine) and is used in anesthesia.

Considering that ketofol and its efficacy has been observed among patients, we have aimed to compare the effects of ketofol and thiopental sodium on the patients undergoing dilation and curettage.

Methods and Materials

This study was approved by ethical committee of Ardabil University of medical sciences (1395.88) and written informed consent was obtained from all subjects, a legal surrogate, or the requirement for written informed consent was waived by ethical committee. The clinical trial with the IRCT2017031923559N9 code (Somaiyeh Matin, 2017.4.24) was registered before patient enrollment authors. This randomized controlled clinical trial was conducted before on patients with missed or incomplete abortion undergoing dilatation and curettage. In this study, 150 patients aged over 16 years and candidates for dilation and curettage with ASA class 1 and 2 were enrolled after obtaining informed consent. Patients with a history of susceptibility to propofol and other intravenous anesthetic drugs, patients with substance abuse, alcohol and psychotropic drugs, as well as patients with gastrointestinal ulcers, kidney disease or hypertension, and hypertension, osteopenia and osteoporosis, and uncontrolled hypertension were excluded. The patients were randomly classified into two groups and placed in two blocks

A and B. Group A or Group 1 were the ketofol group and group B or Group 2 were the thiopental sodium group. The preparation of the drugs was carried out by the anesthesia nurses, and after delivery of the syringes, they were covered with a white label. The drugs were administered by an anesthesiologist who did not know the drug content. In both groups, the patients in the operating room underwent cardiopulmonary monitoring. Then, the appropriate intravenous route was established, and the patients were hydrated, and received oxygen by facemask. Midazolam 0.05 mg / kg, fentanyl 1 μg / kg, and lidocaine 1 mg / kg for each patient were administered.

Subsequently, the first group received ketofol (which was mixed with 2: 1 propofol and ketamine in a syringe), and the second group received thiopental sodium 3 mg / kg body weight. The medication injection rate was 10 mg / sec. Any change in the hemodynamics or respiratory distress including the occurrence of apnea or hypotension, desaturation and the need for respiratory support were recorded in both groups. Eventually, after completion of surgery and transfer to the recovery room, the patients were questioned about satisfaction and anesthesia. All patient information was completed by the anesthesiologist. Finally, all the data was entered into the SPSS v18 statistical program and the data was analyzed. In this study, the t-test and chi-square test were used and P value less than 0.05 was considered significant.

Results

In this study, 150 patients were evaluated in two groups (the first group receiving the ketofol and the second group receiving the thiopental sodium). The mean age of the patients in the first group was 31.82 ± 9.18 years and in the second group was 33.64 ± 11.36 years (P = 0.258).

The incidence of apnea and the need for respiratory support in the thiopental sodium group were higher than the ketofol group (Table 1). Also, the mean duration of apnea in the first and second groups were 50.75 ± 27.77 and 99.22 ± 58.17 seconds, respectively (P <0.001). After recording the systolic, diastolic blood pressure and heart rate before and after induction did not show significant differences in the two groups (Table 2), but in each group, there were significant differences in the vital signs (Table 3). In this study, no cases of hypotension and bradycardia were reported. Awakening during anesthesia showed no significant difference in the two groups, but the amount of drug re-administration during anesthesia was significantly lower in the ketofol group than in the other group (P = 0.016) (Table 1). The mean arrival time of the Aldrete score was 9 and recovery in the ketofol, and thiopental sodium groups were 13.21 ± 3.13 and 19.12 ± 21.5 minutes, respectively (P <0.001). Drug complications in Group A were higher than Group B, but the satisfaction of patient and surgeon for the anesthetic level did not show any significant difference in the two groups (Table 1).

Table 1

Different variables in both groups before and after induction

Table 2

Signs of vital signs in both groups before and after induction

Table 3.

Signs of vital signs of patients before and after the induction by the prescribed medication

Discussion

Various studies have demonstrated that the effect of the combination of propofol and ketamine for the induction of anesthesia is different when injected by a syringe due to different kinetic effects on each other, and the combined drug (Ketofol) produces more effective sedative effects⁷.

In the study by Sawas et al., 52% of the recipients of ketofol and 73% of the propofol recipients experienced respiratory supplements (P = 0.035) ⁸. In a study by Goh et al., the incidence of apnea in propofol (3.3%) was lower than ketofol, and in ketofol (6.3%) was less than fentanyl + propofol (23.1%)⁹. Frey et al. reported respiratory suppression in propofol recipients more than cofactor recipients¹⁰. Jalili, in his meta-analysis study also stated that ketofol can significantly reduce respiratory complications, including depression of the respiratory system¹¹. However, in the study by David and colleagues, there was no significant difference in the incidence of apnea in propofol and ketofol¹². In this study, it was found that the incidence of apnea and the need for respiratory support in the thiopental sodium recipients was higher than that of ketofol. Its incidence in this study was more than other studies, which is probably due to the definition of apnea (respiratory discontinuation of 10 seconds) in this study and its difference with other studies. In their study, Ustun et al. studied the effects of ketofol (0.5 mg/kg) and thiopental (3 mg / kg) on MRI candidates; they observed that the heart rate decreased in both groups. However, there was no significant difference between the two groups in relation to each other¹³. Gholipour et al. also stated that ketofol produces a more stable hemodynamic than the other two groups (etomidated, thiopental + ketamine)¹⁴. Also, Garg et al. reported the ketamine and propofol combination as the best combination for the hemodynamic stability of patients during anesthesia¹⁵. Saleem et al. reported the hemodynamic stability in ketofol as more than in propofol and thiopental¹⁶. The combination of propofol and ketamine has a high degree of hemodynamic stability in other studies by Furuya et al., Ghatak et al., Goh et al., and Ozgul et al. In this study, despite the fact that there was a decrease in blood pressure and heart rate in both groups, no hemodynamic instability was reported, and all patients had stable hemodynamic parameters^9,17,18,19. Like the previous studies, the two drugs, ketofol and thiopental, showed decreased but stable vital signs.

In a study by Ustun et al., the duration of sedation was 36.2 minutes for ketofol recipients and 24.24 minutes for the thiopental sodium patients, which was statistically significant¹³. The duration of hospital stay was 20.4 minutes in the ketofol group and 4.9 minutes in the thiopental group, respectively. In a study by Del Pizzo et al., the duration of sedation was 20 minutes in the propofol group (propofol + ketamine with separate infusion) and recovery time was 18 minutes. In the ketamine group, it was 19 minutes (P = 0.469) and the recovery time was 11, 9, and 12 minutes (P = 0.704)²⁰. A study by Coulter et al. compared proportions of ketamine and propofol in the ketofol drug and reported that a ratio of 1 to 3 ketamine to propofol was appropriate in short procedures (5 to 20 minutes), and by administration of this drug can be prevented from multiple injections with a ratio of 1 to 4. But the injection of ketofol with a ratio of 1 to 4 can increase recovery time to over 20 minutes²¹. In a study by Frey et al., the sedation time in recipients of ketofol and propofol was 164 and 235 seconds, respectively. In this study as in other studies, the need for re-administration of ketofol was less than thiopental. On the other hand, the ketofol recipients had a shorter duration of recovery¹⁰.

Regarding side effects, Sawas et al. reported that ketofol has fewer side effects than propofol, and it is generally accepted as a better anesthetic drug⁸. Gholipur et al. also reported that 15% of recipients had muscle contractions, and 27.5% had nausea and vomiting while receiving ketamine + thiopental (with separate infusion), 20% had muscle contractions, and 7.5% had nausea and vomiting during surgery, while the patients receiving ketofol did not have any side effects¹⁴. Jalili et al. reported that ketofol had significantly fewer complications than other anesthetic drugs, including hallucinations, muscle rigidity, nausea, and vomiting¹¹. A review of other studies has found that propofol in patients reduces nausea and vomiting; the mechanism of this event is not well understood²², but its adjuvant effects or its weak antagonistic effects on the subcortical route can be considered²³.

Conclusion

The results of this study showed that ketofol is a better drug than thiopental for the induction of anesthesia, reducing the need for medication, the incidence of apnea, and the complications of anesthesia.

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