Turkish Neurosurgery 3: 110 - 113. 1993 Kiliç: IntraventriClllar Morphine Therapy In Cancer

Intraventricular Morphine Therapy In Cancer Pain

KA YA KILIÇ. ALAIN CZORNY, BEHIç TÜMER. MAHIR TEvRüz

Haydarpasa Numune Hospital. Department of Neurosurgery. IstanbuL. Türkiye (KK. BT. MT)Service de Neurochirurgie. CHU e Besancon - France (Ae)

Abstract : The authors study the effectiveness and complicationsof intraventricular morhphine therapy in the treatment of preter­minal cancer pain and compare it with other central and systematicadministarions of morphine.

In this series of 35 patients. intraventricular morphine therapywas used when complications of peridural morphine therapydevelop or when high dose morphine application by the systematic

INTRODUCTION

Morphine therapy is used as the W.H.O. alsa sug­gests, after non-opioid analgesics and weak apiodis(Codeine) have been tried and a systematic methodused in the administration of morphine: per os. LM..LV. or S.c. The dos e is increased once tolerance

develops and as this becomes insufficient or side ef­fects of the morphinotherapy develop. other "cen­tral" methods are employed Le. epiduraL. intrathecaL.intraventricular. The morphine reservoir has madesuch use of morphine more widespread.

MATERIAL AND METHODS

Our study examined the results of intraventricularmorphine therapy in intractable cancer pain in 35 pa­tients in the preterminal stage. The sex distributionof the patients in the series showed a dear majorityof males: one female compared with 34 males. Wewere not able to explain this difference and have notencountered anything similar in the literature.

Table I shows the distribution of the primaryneoplasm in 35 cancer patients.

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method had no effect. The quality of analgesia was assessed as"perfect" in 82 % of the cases. The average hospitalizaion periodwas 2 days. All other systematic sedatives. analgesics and an­tidepressants were stopped and the initial dose of o. img/day ofmorphine never subsequently exceeded 0.2-5 mg)day.

Key Words: Intraventricular morphine. Pain. Cancer.

Table i. Dustribution of Primary Neoplasm:

DISTRIBUTION OF PRIMARY NEOPLASM:HEAD AND NECK: 2iLUNGS: IIPROSTATE: 2BREAST: i

Intraventricular morphine therapy was employedin all 35 when:

- Systematic morphine was insufficientregardless of the high dosage.

- One of the known complications of periduralmorphine therapy was encountered (inflammation.infection. rejection of the catheter) or

- when preterminal cancer pain did not allowsurgical interception ofthe nociceptive tractus (cordotomy. radicotomy).

Table II shows the treatment and the dosagestried on the group before the morphine reservoir. In5 of the LO patients fitted the epidural catheter. thecatheter was rejected. The daily morphine dosagegiven to these patients varied between 6-24 mg.

Turkish Neurosurgery 3: 110 - 113. 1993

Table II. Treatments And Dosages Tried BeforeThe Morphine Reservoir:

EPIDURAL CATHETER (6 mg-24 mg/day morphine) : LO cases

MORPHINE SYRUP (30 mg-240 mg/day)and/or

OEXTROMORAMIDE (3-20 TABLETS/OA Y PALFIUM): 19 cases

LEVOMEPROMAZINE (Nozinan) or

FLUNITRAZEPAM (Rohypnol) orPENTAZOClNE (Fortal) and/orOEXTROPROPOXYPHENE (Propofan) 6 cases

Major analgesics such as morphine syrup anddextromoramide proved ineffective in 19 casesa1though given in high doses.

Morphine reservoirs were placed in the other sixpatients when numerous sedatives. antalgics andneuroleptics proved in effective in stopping the pain.when changing from systematic morphine therapyto the intraventricular morphine reservoir. 0.1 mg ofintrathecal morphine chlorhydrote was given andchanges in the pain of the patient were observed. Itwas discovered that pain responding to intrathecalmorphine benefits from the morphine reservoir.

The technique for placing the intraventric1uarmorphine reservoir is identical with that used in ven­tricular puncture: It is based on puncture of the fron­tal ham of the lateral ventric1e under sterile

conditions and neuroleptanalgesia or via a burr haledrilled 3 cm in front of the coronal suture and 3 cm

lateral to the midline. The drug placed in the res er­voir is 0.1 mg/ml concentration morphinechlorhydrate. The total volume should not exceedthat of the reservoir. namely 3 mL.

RESULTS

The inital dosage in our group was relatively law.usualiy 0.1 mg/day. and between 0.2-5 mg/day at theand of the treatment.

The longest and shortest effective treatmentlasted 195 and 3 days respectively with an averageof 51 days.

Table III shows the early complications en­countered in 35 patients. The quality of analgesia wasassessed as "perfecC in 29 cases (82%): no pain wasobserved in these patients even though all antalgics.sedatives and antidepressants had been discon­tinued.

Kiliç: Intraventricular Morphine Therapy In Cancer Pain

Table III. Early Complications Encountered In 35Patients

- Respiratory depression : O

- Retention of urine : O

- Convulsions : 2- Infections :2

- Regressive hemiparesis : 2- Haematoma : O

- Mild intoxication (myosis. haliucination) : 2

- EXITUS : O

The average period of hospitaliazion was 2 days.after which the patients were sent to the first depart­ment of reference and then discharged to theirhomes. Subsequent injections were administeredeither by a nurse or one of the family after detailedinstructions.

The side effects of a method used to treat painin cancerology should be minimal and the analgesicefficiency maximal. Thus. intraventricular morphinetherapy is superior to other methods in many ways:

- The analgesia was highly superior in terms ofduration and quality: the intraventricularmethod provided analgesia with 2 times lessmorphine than the intrathecal and 5 times lessthan the epidural method.

In same cases 1000 times less morphine wasneeded than that used in the systematic method.Analgesia was observed throughout the entire body.especially on the face. thus it is very useful in Headand Neck caneers.

- The minimal and even lack of side effects pro­vide the patient with physical andpsychological comfort. "Respiratory depres­sion" which is a feared complication of the in­trathecal method was not observed even in itsweakest form.

- It is possible to continue the treatment at homebecause of the absence of respiratory depres­sion. the effectiveness of sm all doses and fewother side effects.

- Injections into the reservoir with hypodermicneedles are painless. easily applied and do notinterfere with the autonomy of the patient. Thebath and dressing problem s of a permanentperidural catheter are absent.

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Turkish Neurosurgery}: 110 - ll}. 199}

DlSCUSSION

Mu. delta. kappa. epsilan and sigma recep tar ssensitive to morphine are found on the medullaspinalis and the brain stern. These are especiallydense:

- On the substantia gelatinosa of Luigi Rolandasituated in the dorsal ham of the medulla spinalis.

- In the periventricular and periaquaductal graymatter and

- In the cingular. fronto-basal and hypothalamicregions of the limbic system. (8. 9. 17. 18. 21. 22).

Marphine directly applied to the central nervoussystem reaches these receptors along the shortestroute. Furthermore a big portian of it is notmetabolized and inactivated in the liver like mor­

phine applied systematically thus "longer and moreeffective" analgesia is provided with "much smallerdoses". (3. 4. 5. 7. 12. 13. 14. 15. 19).

The scarcity of side effects such as diuresis.pruritus. constipation. bradycardia. hypertension andnausea and especially absence of respiratory depres­sion are among the advantages of intraventricularmorphine therapy. The reason for the higher frequen­cy of respiratory depression in intrathecal morphinetherapy is that the flow directian of the eS.F. causesthe bulboprotuberential effect to be more intense andfaster.

During the central and peripheral stages of pain.morphine takes effect by increasing the analgesicpower of the enkephalines (i. 6. 10. ll). The centraleffect mechanism is by activation of the bulbo-spinalserotoninergic deseending inhibitor fibrils. Peria­quaductal gray matter is rich in enkephalines andopium receptors hich are connected to the beginningof the serotoninergic inhibitor pathays in the brainstern. this descending pathay activates the in­temeurons in the substantia gelatinosa of Rolanda andthus prevents the release of neurotransmitter of pain.subtance P by the thin C fibres.

In the periphery. like the enkephalines. morphineis attached to the morphine receptors in the medullaspinalis substantia gelatinosa and prevent the releaseof substance P. The accepted opinion is that of knonmorphine receptors. the mu is related to the antalgiceffects and delta and kappas to other side effects.

Intraventricular morphine in small doses blocksthe mu receptors with an antalgic effects. But the side

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Kiliç: 1ntraventricular Morphine Therapy In Cancer Pain

effects are slight because it does not black the deltaand kappa receptars. On the other hand. in morphinetreatment by other methods doses to black all thereceptors are needed and the risk of side effects andrespiratory depression is increased. Although thepercentage of pain occurrence varies depending on thestage of the tumour. a global pain ratio of 510/0 hasbe en reported.

Pain frequency is increased to an average 75 % inadvanced terminal patients (2).Relieffrom pain shouldbe regarded as the most natural right of all cancer pa­tients and a pain therapy respecting this right shouldbe used. Drugs are the basis of the cancer pain treat­ment Strong opioids such as morphine are found inthe last step of the three-step analgesic treatment sug­gested by the .RO. Pain is no longer regarded as a"rule of fate" and physicians are approaching this sub­ject in a more scientific manner, but the manner inhich stupefadents are used and the number of patientsbenefitting from them is still insuffident. An analysisof 12 studies done in developed countries involving2600patients has shown that over 50%of the patientsdo not receive suffident pain treatment (16).

CONCLUSION

Cancer pain is intense. organic. and constantthrough continuous hyperstimulation and has impar­tant psychological consequences. Pain surgery can beconsidered for patients with pa int hose life expectan­ey is long enough (at least 1 year) to justify it. (6. 20).For this reason. intraventricular morphine is an effec­tive and law risk altemative to surgical interruptionof pain pathways in preterminal cases. It should beconsidered especially in cases here dassical methodsprove ineffective in cancer pain of supradiaphragmaticlocatization. However this treatment should be

employed befare the terminal stage and especiallybefore dependency on opioids develops. In smilarpairi of infradiaphragmatic cancer. our choice is a sub­cutaneous morphine reservoir with a periduralcatheter. when the required conditions are met.placement of an intraventricular morphine reservoirseems to be the preferred method for the followingreasons:

1. The quality of analgesia2. The perfect tolerance3. Comfort

4. The law dosage of required morphine and5. The scarcity of side effects.

Turkish Neurosurgery 3: 110 - 113, 1993

Correspondence : Kaya Kiliç M.D.Numune Hospital.Nörosirürji KlinigiÜsküdar· IstanbuUTürkiye

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