Ketamine 정주에 의한 선행진통 효과

Abstract

[한글]

수술에 의한 말초 조직 손상은 화학적 매개체를 분비 시켜 말초 감작을 일으키고, 지속적인 말초 침해 수용체의 흥분 전달은 wide dynamic range(WDR)뉴우론의 탈분극 상태를 유지 시켜 중추 감작을 형성하게 되므로써 술 후 통각과민 상태를 야기한다. N-methyl-D-aspartate 수용체 길항제는 강한 진통 작용뿐 아니라 중추 감작의 유도를 차단 및 예방하는 효과가 있다. 본 연구는 NMDA 수용체 길항효과를 갖는 ketamine을 수술 전 및 수술 중 지속 주입했을 때 선행진통 효과가 있는 지를 알아보고자 하였다.

자궁근종으로 전자궁적출술이 예정된 60명의 환자를 대상으로 무작위로 두군으로 나누었다. 마취 유도 후 활력증후가 안정되면, 실험군은1 mg/kg의 ketamine을 정주하고 0.01 mg/kg/min으로 복막을 닫을 때까지 지속 주입하였고 대조군은 동량의 생리식염수률 사용하였다. 복막을 닫기 시작하면 0.05 mg/kg의 morphine 초회량을 투여하고 0.3mg/ml의 희석한 morphine으로 정맥내 자가통증조절 장치를 사용하여 1ml/hr로 기본 지속주입하였으며 10분에 한번 1 ml의 추가용량이 투여되도록 하였다. Morphine의 총 소모량과 휴식 시와 운동 시의 통중점수(Visual Analogue Scale)를 술 후 1, 3, 6, 9, 12, 24, 36, 그리고 48시간에 측정하고 부작용을 관찰하였다.

휴식시 통증점수는 술 후 1, 3시간과 24, 36, 48시간에 ketamine을 투여한군(실험군)에서 saline을 투여한 군(대조군)보다 유의하게 낮은 점수를 나타내었다. 운동 시 통중점수는 술 후 1,3시간과 12,24,36,48시간에서 실험군이 대조군에 비하여 낮았다. 술 후 투여

된 morphine의 총량은 술 후 1,3,6,9, 12,24,36, 그리고 48시간 모두에서 실험군이 대조군에 비해 20-50% 감소하였다. 불충분한 통증 조절로 meperidine을 투여받은 횟수는, 대조군에서는 16명이 21회 실험군에서는 1명이 2회로 유의한 차이를 보였다. 치료를 요하는 오심, 구토를 보인 환자는 대조군이 많았다. 실험군에서는 10명이 두통을 호소하여 8명이 치료를 받은 반면, 대조군에서는 두통을 호소한 예가 없었다. 그외에 소양감, 요통, 악몽 등의 빈도는 두 군간에 유의한 차이를 보이지 않았다.

결론적으로 술 전 및 술 중 지속적 정맥투여한 ketamine은 술 후 통증점수를 감소시키고 통증 조절을 위한 morphine 소모량을 감소시켰으므로 선행진통효과가 있다고 생각된다.

The preemptive analgesic effect of intravenous ketamine

Jeong Yeon Hong

Department of Medicine The Graduate School, Yonsei University

(Directed by Associate Professor Wyun Kon Park)

Surgical injury provokes two kinds of modification in responsiveness of the

nervous system: peripheral sensitization, a reduction in the threshold of

nociceptor afferent peripheral terminals, and central sentsitization, an

activity-dependent increase in the excitability of spinal neurons. Preemptive

treatment with ketamine, a noncompetitive NMDA antagonist, may prevent

establishment of postoperative hypersensitivity by blocking the sensory input that

induces the central sensitization. The aim of this study was to determine if

continuous preemptive administration of intravenous(IV) ketamine decreases

postoperative pain in comparison with saline.

Sixty informed patients (ASA physical status 1) scheduled far elective abdominal

hysterectomy were randomly divided into two groups of equal size and studied in a

double-blind manner, Before surgical incision, patients in the ketamine group were

given 1mg/kg of ketamine followed by IV infusion of 0.01 mg/kg/min. which was

discontinued at peritoneal closure. The patients in Ihe saline group were given

equal volume of saline instead of ketamine in the same manner. IV morphine

patient-controlled analgesia(PCA) was started in all patients at peritoneal

closure. The PCA device(Medex Walkmed) was programmed to deliver a depend of O.3 mg

of diluted morphine with a 10 min lockout time. The basal infusion rate was set at

0.3 mg/hr after initial bolus dose of 0.05 mg/kg of morphine. Visual Analogue

Scale(VAS) pain scores and total morphine consumption were recorded at 1, 3, 6, 9,

12, 24, 36, and 48 hours postoperatively. The side effects and the treatments were

also recorded.

VAS pain scores at rest were significantly less in the ketamine group than saline

group at 1, 3, 24, 36, and 48 hr postoperatively. On the other hand, VAS at moving

status were less in the ketamine group at 1, 3, 12, 24, 36, 48 hr postoperatively.

Patients in the ketamine group had significantly lower morphine consumption

throughout the study period, about 20-50% reduction in postoperative total morphine

was observed. The incidence of requests for additional analgesics due to

unsatisfactory relief of pain was less in the ketamine group than saline group.

Only ketamine group experienced severe headache(10 cases), while the incidence of

vomiting was significantly higher in saline group. There were no intergroup

differences in other side effects such as pruritus, bad dream, and backache.

These results suggest that preemptive continuous IV ketamine decreases

postoperative pain intensity and IV morphine requirement, and its action lasts

longer than the normal expected duration of action of ketmine.

[영문]

Surgical injury provokes two kinds of modification in responsiveness of the nervous system: peripheral sensitization, a reduction in the threshold of nociceptor afferent peripheral terminals, and central sentsitization, an activity-dependent increase in the excitability of spinal neurons. Preemptive

treatment with ketamine, a noncompetitive NMDA antagonist, may prevent establishment of postoperative hypersensitivity by blocking the sensory input that induces the central sensitization. The aim of this study was to determine if

continuous preemptive administration of intravenous(IV) ketamine decreases postoperative pain in comparison with saline.

Sixty informed patients (ASA physical status 1) scheduled far elective abdominal hysterectomy were randomly divided into two groups of equal size and studied in a double-blind manner, Before surgical incision, patients in the ketamine group were given 1mg/kg of ketamine followed by IV infusion of 0.01 mg/kg/min. which was discontinued at peritoneal closure. The patients in Ihe saline group were given equal volume of saline instead of ketamine in the same manner. IV morphine patient-controlled analgesia(PCA) was started in all patients at peritoneal closure. The PCA device(Medex Walkmed) was programmed to deliver a depend of O.3 mg of diluted morphine with a 10 min lockout time. The basal infusion rate was set at 0.3 mg/hr after initial bolus dose of 0.05 mg/kg of morphine. Visual Analogue Scale(VAS) pain scores and total morphine consumption were recorded at 1, 3, 6, 9, 12, 24, 36, and 48 hours postoperatively. The side effects and the treatments were also recorded.

VAS pain scores at rest were significantly less in the ketamine group than saline group at 1, 3, 24, 36, and 48 hr postoperatively. On the other hand, VAS at moving status were less in the ketamine group at 1, 3, 12, 24, 36, 48 hr postoperatively.

Patients in the ketamine group had significantly lower morphine consumption throughout the study period, about 20-50% reduction in postoperative total morphine was observed. The incidence of requests for additional analgesics due to unsatisfactory relief of pain was less in the ketamine group than saline group.

Only ketamine group experienced severe headache(10 cases), while the incidence of vomiting was significantly higher in saline group. There were no intergroup differences in other side effects such as pruritus, bad dream, and backache.

These results suggest that preemptive continuous IV ketamine decreases postoperative pain intensity and IV morphine requirement, and its action lasts longer than the normal expected duration of action of ketmine.