Abstract
The optimal site to administer opioids e.g. morphine is as close as possible to the opiate receptor site (spinal cord) by the intrathecal route, as it is the place of effectiveness. To improve the clinical effectiveness of intrathecal morphine two strategies
are proposed: 1. to lower the intrathecal
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dose of morphine and thereby reduce the supraspinal adverse effects while maintaining
the analgesic effects; 2. further research to synthesize highly selective endorphin mimetic drugs with a minimum of side effects.
We hypothesized that low doses of intrathecal morphine might probably result in similar pain relief scores but might minimize
the incidence of adverse effects. The first study was designed to determine the optimal intrathecal dose of morphine in total hip
surgery. The optimal intrathecal dose was defined as the dose, which provides effective analgesia with minimal side effects
during 24 h after total hip surgery. Patients (n=143) scheduled for total hip surgery were randomized to four double-blinded
groups with a standardized bupivacaine dose but different doses of intrathecal morphine: group I, 0.025 mg; group II, 0.05 mg;
group III, 0.1 mg; and, group IV, 0.2 mg. Pain scores, intravenous morphine intake {patient controlled analgesia (PCA)} and
morphine related side effects (respiratory depression, postoperative nausea and vomiting, itching, urinary retention) were
recorded for 24 h after surgery. Excellent postoperative pain relief was present in all groups. The highest pain scores were found
in group I. The mean use of systemic morphine administered by PCA infusion pump was: 23.7 mg, 17.8 mg, 10.9 mg and 9.9 mg,
in group I, II, III, and IV, respectively (p<0.01, group III and IV versus group I). We conclude that 0.1 mg intrathecal morphine is
the optimal dose for pain relief after hip surgery with minimal side effects. A second study evaluated the questions: firstly, to
what extent do spinal opiates contribute to PONV (post operative nausea and vomiting); and, secondly, how effectively can
metoclopramide reduce the incidence of PONV after intrathecal administration of morphine. All patients were scheduled to
undergo major joint surgery of the lower limb. The patients were allocated to three groups. Group I (n=200): intrathecal
anesthesia was induced by administration of 20 mg bupivacaine and 0.2 mg morphine. Group II (n=100): intrathecal anesthesia
was induced using the same dosages and drugs for intrathecal anesthesia, but in addition systemic metoclopramide was
injected in two doses of 20 mg. Finally, for patients in group III (n=100) intrathecal anesthesia was induced by the
administration of 20 mg bupivacaine only. The maximum PONV percentages were 41.1%, 32.7% and 37% in group I, II and III
respectively. The consumption of antiemetics was similar in all groups. The number of patients who needed one or more
additional antiemetics during the first 24 hours after surgery was 112 (56.6%), 57 (58%) and 60 (60%) in group I, II and III,
respectively. Administration of metoclopramide did not reduce the overall incidence of PONV. Our study shows no relationship
between the use of 0.2 mg intrathecal morphine and the incidence of PONV during 24 hours postoperatively. The third study
was designed to determine whether low doses of intrathecal morphine still result in itching and it evaluates the outcome of
using standardized treatment with promethazine and - for intractable itch - naloxon. Patients (n=143) scheduled for total hip
surgery were randomized to four double-blinded groups with a standardized bupivacaine dose but different doses of intrathecal
morphine: group I, 0.025 mg; group II, 0.05 mg; group III, 0.1 mg; and, group IV, 0.2 mg (same patients as Chapter 3). The
presence or absence of itching was noted every three hours for a twenty-four hour period. When requested by the patient, the
standard procedure for treatment was initiated. The incidence of itching was: Group I: 14.3%; Group II: 21.6%; Group III: 48.6%;
and, Group IV: 61.7%. Itch was treated by administering promethazine intramuscularly in 2,9% (Group I); 8,1% (Group II); 10.8%
(Group III); and, 8.9% (Group IV) respectively. Only in group IV there was 1 patient who needed naloxon to treat itching. The
incidence and severity of itching is a dose related side effect in the dose range of 0.025 – 0.2 mg of intrathecal morphine. Itching
even occurs after the low doses of intrathecal morphine, but symptoms vanish after promethazine 25 mg intramuscularly.
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