Analgesic Efficacy and Adverse Effects of Intrathecally Administered Neostigmine in Patients ...

106 Pages·2006·1.61 MB·English

ﻢﻴﺣﺮﻟﺍ ﻦﲪﺮﻟﺍ ﷲﺍ ﻢﺴﺑ
University of Khartoum
The Graduate College
Postgraduate Medical and Health Studies Board

Analgesic Efficacy and Adverse Effects of Intrathecally
Administered Neostigmine in Patients Submitted to
Spinal Anaesthesia

By

Dr. Abdullah Yahia Al-sailamy
M.B.B.S King Saud University – Riyadh, K.S.A

A thesis submitted in partial fulfillment for the requirements of
the Degree of Clinical M.D. in Anaesthesia and Intensive Care

April 2005

SUPERVISOR

Dr. Kamal Mohammed El-Hassan El-Mubashar
Associated Professor of anaesthesia,
Department of Anaesthesia,
University of Khartoum
DEDICATION

♦ To my amazing parents

♦ To my wife, Dr. Belques, for being so supportive and
understanding

♦ To my teachers, colleagues and friends for their help and
inspiration
TABLE OF CONTENTS
Page
Acknowledgement……………………………..………..…I
List of abbreviations………………………………………II
List of tables……………………………………...………III
List of figures…………………………………………..…IV
English abstract……………………………………………V
Arabic abstract……………………………………….….VII

Chapter 1
Introduction…………………………………………..… 1
Literature review
(cid:131) Spinal anaesthesia………………………………….…. 4
(cid:131) Spinal cord physiology and pharmacology of pain...… 23
(cid:131) Spinal Neostigmine………………………………...….30
(cid:131) Local anaesthetics……………………………………..34
Objective……………………………………………… 39

Chapter 2
Patients and methods…………………………………. 41

Chapter 3
Results………………………………………………… 48
Tables………………………………………….……… 52
Figures………………………………………………… 57
Discussion…………………………………………….. 73

Chapter 4
Conclusions…………………………………………… 80
Recommendations…………………………………….. 81
References………………………………………….…. 83
Appendix………………………………………….…… 93
ACKNOWLEDGEMENT

I would like to express my indebtedness and gratitude to my
supervisor, Dr. Kamal Mohammed El_Hassan El_Mubashar, associated
professor of anaesthesia, department of Anaesthesia, University of Khartoum
for his great help and tolerance in accepting to supervise this work and for his
continuous invaluable guidance and support.
I am also grateful to Dr. Irene Sobhi, assistant professor of
anaesthesia, department of anaesthesia, University of Khartoum, for her kind
help.
Thanks and gratitude are extended to anaesthetic and nursing staff at
Khartoum Teaching and Soba University Hospitals for the great help and co-
operation in data collection.
I would like to thank all my patients for their acceptance and pleasant
co-operation.
LIST OF ABBREVIATIONS

ASA American Society of Anesthesiologist
ACh Acetylcholine
CSF Cerebrospinal Fluid
GA General Anaesthesia
IT Intrathecal
KTH Khartoum Teaching Hospital
LA Local anaesthetics
PDPH Post dural puncture headache
SA Spinal Anaesthesia
SC Spinal Cord
SUH Soba University Hospital
TNS Transient Neurological Symptoms
VAS Visual Analogue Scale
LIST OF TABLES

Page
Table 1: Demographic data of the patients ………….……....52
Table 2: Level to pinprick at 5 and 10 minutes ……………..52
Table 3: Postoperative Analgesia.….….…………………….53
Table 4: Need for postoperative analgesia ……………….…53
Table 5: Intraoperative hypotension ………………………..54
Table 6: Intraoperative bradycardia…………………………54
Table 7: Intraoperative Nausea ………………………..……55
Table 8: Intraoperative Vomiting…………………………...55
Table 9: Motor block……......................................................56
Table 10: Bowel movement……………………………..….56
LIST OF FIGURES

Page
Figure 1: Demographic data of the patients (age).................57
Figure 2: Demographic data of the patients (ASA)...............58
Figure 3: Demographic data of the patients (sex)…….…….59
Figure 4: Level to pinprick at 5 and 10 minutes....................60
Figure 5: Intraoperative data.…............................................61
Figure 6: Time of postoperative analgesia……………….....62
Figure 7: 24-hour vas pain assessment…………………......63
Figure 8: Time to first rescue analgesia................................64
Figure 9: patients requesting postoperative analgesia……....65
Figure 10: Intraoperative hypotension and bradycardia…....66
Figure 11: Time to first hypotension and bradycardia….…..67
Figure 12: Intraoperative nausea and vomiting………....…..68
Figure 13: Time to first nausea…………………….…...…..69
Figure 14: 24-hour VAS nausea…………….……………...70
Figure 15: Number of patients received metochlopromide
and ondansetron………………………….…………….........71
ABSTRACT

Background:
Spinal administration of neostigmine as a non-opioid analgesic appears
to provide a potent, long lasting analgesia. The present study was designed to
evaluate the effects of the addition of different doses of neostigmine on the
characteristics of spinal anaesthesia using bupivacaine, and to assess their
postoperative analgesic efficacy and safety in patients undergoing infra-
umbilical surgery under spinal anaesthesia.

Methods:
In this prospective study, we studied sixty Sudanese patients, classified
as class 1 and 2 according to the American society of anesthesiologist (ASA),
in the age group 19 - 65 year old. They were scheduled for infra-umbilical
surgery under spinal anaesthesia. Patients were randomly allocated to one of
three groups (n=20 each): group one received intrathecal bupivacaine 15 mg,
and group two received intrathecal bupivacaine 15 mg and neostigmine 50
µg, and group three received intrathecal bupivacaine 15 mg and neostigmine
100µg. The onset of anaesthesia, the duration of complete postoperative
analgesia, the time to use of the first rescue analgesics, the overall 24-h VAS
pain scores, and the incidence of adverse effects, if any, were recorded for 24-
h post drug administration. Intraoperative and postoperative blood pressure,
heart rate, and oxygen saturation, and total amount of analgesic consumed
overall 24-h, were also recorded.

Results:
Onset of anaesthesia (level to pinprick at 5 and 10 minuets) was
significantly earlier for group 2 and 3 patients compared with group 1
patients. Motor block (time to lift leg) was greatly prolonged for group 3
patients. There was a significant prolongation in the duration of absolute
analgesia between different groups (p < 0.05). Group 3 patients, also showed
a lower overall 24-h VAS pain score and prolonged time to first rescue
analgesics. There was a dose dependent increase in the severity of nausea and
vomiting with highest VAS nausea score in group 3 patients.

Conclusion:
The combination of 50 µg or 100 µg neostigmine with 15 mg of
hyperbaric bupivacaine, given intrathecally, delayed postoperative pain for
4.7 – 6 h and lowered the number of rescue analgesics, in dose dependent
manner. Because the better quality of analgesia was obtained with an
increased (statistically significant differences) in incidence of untoward side
effects, larger samples should be studied before this application can be
routinely used clinically.
ﺔﺣوﺮﻃﻷا ﺺﺨﻠﻣ

: ﺔﺳارﺪﻟا فﺪهو ﺔﻴﻔﻠﺧ
ﺮﻳﺪ(cid:1127)ﺨﺘﻟا ﻲ(cid:1127)ﻓ ﻲﻧﻮ(cid:1127)ﻴﻓأ ﺮ(cid:1127)ﻴﻏ رﺎﻘﻌآ (neostigmine) ﻦ ﻴﻤﻘﻴﺘﺳﻮﻴﻨﻟا لﺎﻤﻌﺘﺳا نأ تﺎﺳارﺪﻟا ﻢﻈﻌﻣ تﺮﻬﻇأ
.ﻢﻟﻷا ﺞﺋﺎﺘﻧ ﻲﻓ ﺮﺒآأ ﺎﺿﺎﻔﺨﻧا ﻰﻟإ ىدأ ﻲﻔﺼﻨﻟا
ﺮ ﻳﺪ(cid:1127)ﺨﺘﻟا ﺺﺋﺎﺼ(cid:1127)ﺧ ﻰ(cid:1127)ﻠﻋ ﻦﻴﻤﻘﻴﺘ(cid:1127)ﺳﻮﻴﻨﻟا رﺎ(cid:1127)ﻘﻋ ﻦ(cid:1127)ﻣ ﺔﻔﻠﺘﺨﻣ تﺎﻋﺮﺟ ﺮﻴﺛﺄﺗ ﻢﻴﻴﻘﺗ ﻮه ﺔﺳارﺪﻟا ﻩﺬه ﻦﻣ فﺪﻬﻟا
ﺔ(cid:1127)ﻈﺣﻼﻣ ﻚﻟﺬ(cid:1127)آو ،(heavy bupivacaine) ﻞ(cid:1127)ﻴﻘﺜﻟا ﻦﻴآﺎ(cid:1127)ﻔﻴﺑﻮﻴﺑ ﻲﻌﺿﻮﻤﻟا رﺪﺨﻤﻟا ﻰﻟإ ﺔﻓﺎﻀﻣ ،ﻲﻔﺼﻨﻟا
.ةﺮﺴﻟا ﺖﺤﺗ ﺔﻴﺣاﺮﺠﻟا تﺎﻴﻠﻤﻌﻟا ﺪﻌﺑ ﻦﻜﺴﻤآ ﻪﻣاﺪﺨﺘﺳا ﻲﻓ نﺎﻣﻷاو ﺔﻴﻟﺎﻌﻔﻟا
: ﺔﺳارﺪﻟا ﺔﻘﻳﺮﻃ
ﻰ(cid:1127)(cid:1127)ﻟوﻷا ﺔ(cid:1127)(cid:1127)ﺟرﺪﻟا ﻦ(cid:1127)(cid:1127)ﻣ ، ﺔﻴﺴ(cid:1127)(cid:1127)ﻨﺠﻟا ﻲﻧادﻮ(cid:1127)(cid:1127)ﺳ (ﻪﻀ(cid:1127)(cid:1127)ﻳﺮﻣو) ﺎﻀ(cid:1127)(cid:1127)ﻳﺮﻣ نﻮﺘﺴ(cid:1127)(cid:1127)ﻟ ﺔ ﻴﻠﺒﻘﺘﺴ(cid:1127)(cid:1127)ﻤﻟا ﺔ(cid:1127)(cid:1127)ﺳارﺪﻟا ﻩﺬ(cid:1127)(cid:1127)ه ﺖ(cid:1127)(cid:1127)ﻳﺮﺟأ
American Society of ) ﻪ(cid:1127)(cid:1127)(cid:1127)(cid:1127)(cid:1127)ﻴﻜﻳﺮﻣﻻا ﺮﻳﺪ(cid:1127)(cid:1127)(cid:1127)(cid:1127)(cid:1127)ﺨﺘﻟا ﻲﺋﺎﺼ(cid:1127)(cid:1127)(cid:1127)(cid:1127)(cid:1127)ﺧأ ﺔ(cid:1127)(cid:1127)(cid:1127)(cid:1127)(cid:1127)ﻴﻌﻤﺟ ﻒﻴﻨﺼ(cid:1127)(cid:1127)(cid:1127)(cid:1127)(cid:1127)ﺘﻟ ﺔ(cid:1127)(cid:1127)(cid:1127)(cid:1127)(cid:1127)ﻴﻧﺎﺜﻟاو
ﻪ(cid:1127)ﻴﺣاﺮﺟ تﺎ(cid:1127)ﻴﻠﻤﻋ ءادﻷ اوﺮﻀ(cid:1127)ﺣ ، ﻪﻨ(cid:1127)ﺳ 65 – 21 ﺮ(cid:1127)ﻤﻋ ﻦﻴﺑﺎ(cid:1127)ﻣ ﺔﻴﺤﺼ(cid:1127)ﻟا ﺔ(cid:1127)ﻗﺎﻴﻠﻟ (Anesthesiologist
.ﻲﻔﺼﻨﻟا ﺮﻳﺪﺨﺘﻟا ﺮﻴﺛﺄﺗ ﺖﺤﺗ ةدرﺎﺑ
ﺖ(cid:1127)(cid:1127)(cid:1127)ﻴﻄﻋأ .ﺎﻀ(cid:1127)(cid:1127)(cid:1127)ﻳﺮﻣ 20 ﺎ(cid:1127)(cid:1127)(cid:1127)ﻬﻨﻣ ﻞ(cid:1127)(cid:1127)(cid:1127)آ ﻲ(cid:1127)(cid:1127)(cid:1127)ﻓ تﺎ(cid:1127)(cid:1127)(cid:1127)ﻋﻮﻤﺠﻣ ثﻼ(cid:1127)(cid:1127)(cid:1127)ﺛ ﻰ(cid:1127)(cid:1127)(cid:1127)ﻟإ ﺎﻴﺋاﻮﺸ(cid:1127)(cid:1127)(cid:1127)ﻋ ﻰ(cid:1127)(cid:1127)(cid:1127)ﺿﺮﻤﻟا ﻒﻴﻨﺼ(cid:1127)(cid:1127)(cid:1127)ﺗو رﺎ(cid:1127)(cid:1127)(cid:1127)ﻴﺘﺧا ﻢ(cid:1127)(cid:1127)(cid:1127)ﺗ
ﺔ(cid:1127)ﻋﻮﻤﺠﻤﻠﻟ ﻦﻴﻤﻘﻴﺘ(cid:1127)ﺳﻮﻴﻧ ماﺮ(cid:1127)ﺟوﺮﻜﻴﻣ 100 و 50 ﻒﻴ(cid:1127)ﺿأو ، ﻂﻘﻓ ﻦﻴآﺎﻔﻴﺑﻮﻴﺑ ﻢ ﺠﻠﻣ 15 ﻰﻟوﻷا ﺔﻋﻮﻤﺠﻤﻟا
.ﻲﻟﺎﺘﺘﻟﺎﺑ ﺔﺜﻟﺎﺜﻟاو ﺔﻴﻧﺎﺜﻟا
ﻢﻟﻷﺎ(cid:1127)ﺑ رﻮﻌﺸ(cid:1127)ﻟا لﺪ(cid:1127)ﻌﻣو ﺮ(cid:1127)ﺧﺁ ﻦﻜﺴ(cid:1127)ﻤﻟ ﺾﻳﺮ(cid:1127)ﻤﻟا ﺐ(cid:1127)ﻠﻃ ﺖﻗو ، ﻦﻜﺴﻤﻟا ةﺪﻣ ، ﻦﻜﺴﻤﻟا ﺮﻴﺛﺄﺗ ﺔﻳاﺪﺑ ﺔﻧرﺎﻘﻣ ﺖﻤﺗ
لﺪ(cid:1127)ﻌﻣ ، ﻂﻐﻀ(cid:1127)ﻟا) ﻰ(cid:1127)ﺿﺮﻤﻠﻟ ﺔ(cid:1127)ﻳﻮﻴﺤﻟ ا تﺎ(cid:1127)ﻣﻼﻌﻟا ﺔ(cid:1127)ﻧرﺎﻘﻣ ﺖ(cid:1127)ﻤﺗ ﻚﻟﺬ(cid:1127)آ . ﺔ(cid:1127)ﻴﻠﻤﻌﻟا ﺖﻠﺗ ﻲﺘﻟا ﺔﻋﺎﺳ 24 لا لﻼﺧ
ةﺪ(cid:1127)(cid:1127)ﻤﻟ ، ﺔ(cid:1127)(cid:1127)ﻗﺎﻓﻹا ﺔ(cid:1127)(cid:1127)ﻓﺮﻏ ﻲ(cid:1127)(cid:1127)ﻓو ﺔ(cid:1127)(cid:1127)ﻴﻠﻤﻌﻟا ةﺮ(cid:1127)(cid:1127)ﺘﻓ لاﻮ(cid:1127)ﻃ (ﻦﻴﺠﺴ(cid:1127)(cid:1127)آﻷﺎﺑ مﺪ(cid:1127)(cid:1127)ﻟا ﻊﺒﺸ(cid:1127)(cid:1127)ﺗ لﺪ(cid:1127)(cid:1127)ﻌﻣو ، ﺲﻔﻨ(cid:1127)(cid:1127)ﺘﻟاو ﺐ(cid:1127)(cid:1127)ﻠﻘﻟا تﺎﺑﺮ(cid:1127)ﺿ
.ﺔﻴﻠﻤﻌﻟا ﺪﻌﺑ ﺔﻋﺎﺳ 24لا ةﺮﺘﻓ لاﻮﻃ رﺎﻘﻌﻠﻟ ﺔﻴﺒﻧﺎﺟ تاﺮﻴﺛﺄﺗ يأ ﻞﻴﺠﺴﺗ ﻢﺗ ﺪﻗو .ﺔﻴﻠﻤﻌﻟا ﺪﻌﺑ ﻦﻴﺘﻋﺎﺳ
: ﺞﺋﺎﺘﻨﻟا
ﺔ(cid:1127)ﺜﻟﺎﺜﻟاو ﺔ(cid:1127)ﻴﻧﺎﺜﻟا ﺔ(cid:1127)ﻋﻮﻤﺠﻤﻟا ﻲ(cid:1127)ﻓ ﻦﻴآﺎ(cid:1127)ﻔﻴﺑﻮﻴﺑ ﻲﻌ(cid:1127)ﺿﻮﻤﻟا رﺪ(cid:1127)ﺨﻤﻟ ا ﺮﻴﺛﺄ(cid:1127)ﺗ ﺔ(cid:1127)ﻳاﺪﺑ ﻦﺴ(cid:1127)ﺤﺗ ﻰ(cid:1127)ﻟإ ﺔﻓﺎﺿﻹا ﻩﺬه تدأ
فاﺮ(cid:1127)ﻃﻷا ﻚ(cid:1127)ﻳﺮﺤﺗ ﺔ(cid:1127)ﻳاﺪﺑ ﻰ(cid:1127)ﻠﻋ ﺾﻳﺮ(cid:1127)ﻤﻟا ةرﺪ(cid:1127)ﻘﻟ لﻮ(cid:1127)ﻃأ ﻦ(cid:1127)ﻣز ﻞﻴﺠﺴ(cid:1127)ﺗ ﻢ(cid:1127)ﺗ ﻚﻟﺬآ . ﻰﻟوﻷا ﺔﻋﻮﻤﺠﻤﻟﺎﺑ ﺔﻧرﺎﻘﻣ
.ﻰﻟوﻷﺎﺑ ﺔﻧرﺎﻘﻣ ﺔﻴﻧﺎﺜﻟاو ﺔﺜﻟﺎﺜﻟا ﺔﻋﻮﻤﺠﻤﻟا ﻲﻓ لﻮﻃأ ﺖﻧﺎﻜﻓ ﺮﻳﺮﺴﻟا ﻦﻋ ﺎﻬﻌﻓرو
ﻪ(cid:1127)ﻟ نﺎ(cid:1127)آ (%0.5) ﻞ(cid:1127)ﻴﻘﺜﻟا ﻦﻴآﺎ(cid:1127)ﻔﻴﺑﻮﻴﺒ ﻟا رﺎ(cid:1127)ﻘﻋ ﻊ(cid:1127)ﻣ ﻦﻴﻤﻘﻴﺘ (cid:1127)ﺳﻮﻴﻨﻟا رﺎ(cid:1127)ﻘﻋ لﺎﻤﻌﺘ(cid:1127)ﺳا نأ ﺪ(cid:1127)ﺟو ﺔ(cid:1127)ﺳارﺪﻟا ﻩﺬه ﻲﻓ
، يﻮﻧﺎ(cid:1127)(cid:1127)ﺜﻟا ﻦﻜﺴ(cid:1127)(cid:1127)ﻤﻟا ﻦ(cid:1127)(cid:1127)ﻣ ﻞ(cid:1127)(cid:1127)ﻗا دﺪ(cid:1127)(cid:1127)ﻋ ﻞﻴﺠﺴ(cid:1127)(cid:1127)ﺗ ﻢ(cid:1127)(cid:1127)ﺗ ﻚﻟﺬ(cid:1127)(cid:1127)آ . ﺔ(cid:1127)(cid:1127)ﻴﻠﻤﻌﻟا ﺪ(cid:1127)(cid:1127)ﻌﺑ ﻢﻟﻷﺎ(cid:1127)(cid:1127)ﺑ رﻮﻌﺸ(cid:1127)(cid:1127)ﻟا ﺮﻴﺧﺄ(cid:1127)(cid:1127)ﺗ ﻲ(cid:1127)(cid:1127)ﻓ ﺎ(cid:1127)(cid:1127)ﻴﺑﺎﺠﻳا اﺮﻴﺛﺄ(cid:1127)(cid:1127)ﺗ
.ﻢﻟﻷﺎﺑ رﻮﻌﺸﻟا ﺪﻨﻋ ﺔﻴﻠﻤﻌﻟا ﺪﻌﺑ ﻰﺿﺮﻤﻠﻟ ةؤﺎﻄﻋا ﻢﺗ يﺬﻟا ،(diclofenac) كﺎﻨﻴﻓﻮﻠﻜﻳد