Philip R. Bromage

Epidural Narcotics for Postoperative Analgesia

Epidural narcotic analgesia was assessed in 66 patients after surgery under epidural and light general anesthesia. Changes of forced expiratory volume in 1 second (FEV,) were measured after upper abdominal or thoracic surgery in 41 patients, and comparisons were made with results in an additional 17 upper abdominal surgery patients who received general anesthesia and muscle relaxants followed by intravenous morphine for postoperative pain relief. Metha- done, 1.0 mg, hydromorphone, 1.0 mg, or morphine sulfate, 5 mg, was administered epidurally and increments were repeated as necessary until satisfactory analgesia was reported, with the following results (mean ± SD): intravenous morphine: latency 3 to 10 minutes, duration 3.1 ± 1.6 hours; epidural methadone: latency 17.2 ± 4 minutes, duration 5.6 ± 2.7 hours; epidural hydromorphone: latency 22.5 ± 6 minutes, duration 9.8 ± 5.5 hours; epidural morphine: latency 36 ± 6 minutes, duration 16.4 ± 7 hours. Duration of action was slightly longer after lower abdominal surgery. Addition of epinephrine 1 /200.000 to the epidural narcotic solutions did not prolong duration. Narcotic requirements for satisfactory analgesia were approximately the same by the intravenous route as by the epidural route and equivalent to 8.5 to 9 mg of morphine. FEV, was reduced to 36.8 ± 13.2% of preoperative control values after general anesthesia and muscle relaxants and to 46 ± 12% of control after epidural and general anesthesia. Intravenous morphine improved FEV, to 45.3 ± 12% of control, whereas epidural narcotics and local anesthetics produced a greater increase of FEV, in the following amounts: epidural local anesthetic to 68.7 ± 9.1% of control and epidural narcotics to 67.1 ± 14.7% of control. Epidural narcotics did not cause sympathetic depression or bladder dysfunction, and analgesia was segmental. We conclude that epidural narcotics in adequate dosage are an effective means for production of prolonged and segmental postoperative analgesia.

Nonrespiratory side effects of epidural morphine.

Ten healthy young male volunteers received in random sequence 10 mg of morphine sulfate intravenously and by lumbar epidural route during two 26-hour study sessions, in order to observe the appearance and resolution of the following side effects: (a) pruritus, (b) nausea, (c) vomiting, (d) urinary dysfunction. With the exception of one subject, who experienced transient (2 hours) nausea, none of the subjects experienced any adverse side effects after the intravenous morphine. However, all subjects experienced some degree of one or more complications, starting 3 hours after the epidural administration: generalized pruritus started at 3.0 ± 0.3 hours (nine of 10 subjects, mean ± SD) and lasted 5.3 ± 4.0 hours. Nausea occurred in six subjects at 4.0 ± 0.6 hours, and lasted for 3.0 ± 2.1 hours; vomiting occurred at 6.3 ± 2.0 hours in five of the nauseated subjects. Urinary retention of varying intensity and duration appeared in nine subjects and required pharmacologic intervention in six subjects. Serum levels of unmodified morphine were measured at various times after administration during both sessions and did not correlate with the incidence or temporal appearance of side effects. Serial evaluation of dermatomal level of hypalgesia to ice and pin scratch demonstrated a progressive spread in the rostral direction after epidural morphine; trigeminal areas were affected by 9 hours in five of the 10 subjects. The stereotyped sequence of side effects after 10 mg of morphine by the epidural route can be interpreted to reflect widespread dispersion of morphine throughout the subarachnoid and ventricular cerebrospinal fluid.

Effect of acute sympathectomy by epidural anesthesia on the canine coronary circulation.

The effects of reversible sympathetic neural blockade of the canine myocardium under control conditions and in the presence of decreased coronary blood flow and after myocardial infarction were investigated in 17 dogs. A multiple-microsphere technique was used to measure distribution of blood flow in the myocardium. Epidural blockade was associated with the following changes in the ratio of endocardial to epicardial blood flow: under control conditions, no change; after 50 per cent decrease in coronary flow, 18 per cent increase in endocardial/epicardial ratio; after myocardial infarction at unrestricted coronary flow, 43 per cent ratio increase; after myocardial infarction and 50 per cent decrease in coronary flow, 76 per cent increase of endocardial/epicardial ratio. These effects appear to be independent of systemic factors, and may result from alterations in tone of transmural resistance vessels. In addition, cervicothoracic epidural blockade resulted in a decrease in systemic pressure and an increase in coronary vascular resistance as myocardial oxygen demand decreased. When systemic pressure was restored these effects were abolished. In the presence of myocardial infarction, epidural blockade had less effect on systemic pressure and left ventricular filling pressure was decreased. With decreased coronary flow, sympathetic blockade redistributed coronary blood flow, favoring the endocardium in both the normal and the infarcted heart.

Influence of Epinephrine as an Adjuvant to Epidural Morphine

The effects of epinephrine 1/200,000 as an adjuvant to epidural morphine were investigated in three healthy male volunteers, during 26-h observation sessions. Peak blood concentrations of morphine were 44 ± 12.9 ng/ml after plain morphine and 13.7 ± 6.7 ng/ml after epinephrine-morphine. Cutaneous hypalgesia was more intense, faster in onset, and longer in duration after epinephrine-morphine than after plain morphine, and analgesia to ice-water immersion of extremities lasted longer. Adverse side effects of pruritus, nausea, vomiting, and difficulty of micturition were also more intense after epinephrine-morphine, and respiratory sensitivity to CO2 was depressed more severely between 6 and 16 h. The results indicated that epinephrine 1/200,000 reduces vascular absorption of epidural morphine and intensifies all the manifestations of cord and brainstem uptake.

The price of intraspinal narcotic analgesia: basic constraints.

AIN RELIEF has always been bought at a price. P Parenteral narcotic analgesia has gone hand-inhand with respiratory depression, as the blood-brain barrier ensured that central respiratory mechanisms and central pain mechanisms received more-or-less equal shares of whatever narcotic was available from the blood compartment. Certain forms of regional anesthesia, especially continuous epidural analgesia, became popular because they could avoid the respiratory cost and relieve pain in a segmental fashion without causing central depression. But, these also exacted a price in terms of complexity of clinical management, as well as the side effects of cardiovascular depression from sympathetic blockade and a high incidence of urinary retention. A third possibility, and a way around these difficulties evolved when narcotics were found to act at the level of the spinal cord (1-3). Animal experiments showed that intense segmental analgesia resulted from small intrathecal doses of narcotics (4). Later, human studies indicated that intense and prolonged segmental analgesia followed intrathecal injection of very small doses of morphine in the range of 0.5 to 1.0 mg (5 ) . At last, the deadlock between analgesia and central depression seemed to be broken, with the promise of extraordinarily effective pain relief safely limited to a chosen segmental area of the body. At first sight, the concept of intraspinal narcotic therapy appears deceptively simple in the following broad terms. The blood-brain barrier is bypassed when narcotics are placed in the cerebrospinal fluid (CSF), and entry into the neuraxis is then a matter of balance between solubility in water and solubility in lipids, as it is with local anesthetics. Specific receptor binding also plays an important role and strong receptor binding contributes further to long duration of action. Analgesia is segmental, just as it is with local anesthetics, but the narcotics provide pure pain relief since their targets, the opiate receptors, are confined to synaptic junctions in the small-cell networks of laminae 1 and 2 of the dorsal horn, a region devoted to modulation of nociceptive input from small primary afferent nerves of unmyelinated Cand myelinated A-delta classification. The CSF can be reached either directly by subarachnoid injection or indirectly by epidural injection and subsequent diffusion through the meninges. The resulting concentrations of narcotic in the CSF are very high and the ratio of CSF to blood concentration is much greater than can be achieved by ordinary parenteral administration (6); this is roughly what is reflected clinically. Analgesia is intense and initially segmental and free of sympathetic, motor, or proprioceptive effects. Moreover, pain relief is remarkably prolonged for up to 24 hours or so when a poorly lipid-soluble drug such as morphine is used. Unfortunately, the overall clinical picture is not quite so simple. Unwanted side effects may arise from variations of pharmacodynamics in four main areas of distribution, namely blood, CSF, neuraxis, and finally at the point of binding at the receptor site itself. The side effects of intraspinal narcotics are frequent, and some are potentially dangerous enough for us to question whether these very promising analgesic techniques should be widey used in a routine fashion without special nursing surveillance. As might be expected, both analgesia and most of the side effects are dose dependent. In practice, severe acute pain often persists until incremental doses of narcotic have been given to a point where the cumulative dose is sufficient both to relieve pain and to precipitate a complication. Pruritus is the least serious but one of the most interesting side effects of epidural narcotics. It has been seen with a number of different narcotics, including fentanyl, meperidine, methadone, hydromorphone, and morphine, and the incidence is dose related. The distribution of itching is not confined to the segmental area of analgesia, but occurs most frequently about the head, neck, and trunk, suggesting that it is related to a generalized modulation of cutaneous sensation rather than to histamine release.

Ventilatory CO2 sensitivity after intravenous and epidural morphine in volunteers.

Ventilatory sensitivity to CO2 was measured at various times (0.5, 1, 3, 6, 10, 16, and 22 h) in 10 healthy young volunteers after 10 mg of morphine sulfate in 10 ml of saline injected intravenously (IVm) or by the epidural route (Em). The two randomized study sequences were completed 2–4 weeks apart. Ventilatory variables studied were resting endtidal CO2 (Petco2) measured before each rebreathing maneuver; slopes of the Ventilatory response curve (s&OV0312;E) and position of the curve, calculated as the ventilation sustained for a fixed stimulus of Petco2 = 54 ton (&OV0312;E54). Additionally, linear regressions were calculated for tidal volumes (VT) and respiratory rates (RR) during the rebreathing test, yielding sVT, VT54, sRR, and RR54. CO2-response curves were maximally depressed following IVm at the 0.5-h study period, while after Em, maximal respiratory depression was at the 6-and 10-h study period. Significantly greater depression after Em was demonstrated between 3 and 22 h by one or more of the following parameters: Petco2, s&OV0312;E, &OV0312;E54, VT54, and sRR. The results indicate substantial differences in magnitude, duration, and characteristics of the depression of the CO2 chemosensitivity between the two modes of administration of morphine, quite separate from the differences observed for serum morphine levels in these volunteers.

Epidural narcotics in volunteers: Sensitivity to pain and to carbon dioxide

&NA; Tolerance to pain and sensitivity to rising concentrations fo inhaled carbon dioxide were measured before and after administration of metadone, 5 mg, or hydromorphone, 0.5 mg, by the intravenous route and by epidural injection in the lumbar or upper thoracic region in 5 subjects. Tolerance to periosteal pressure, cutaneous electrical stimulation and the cold pressor response to ice‐water immersion were measured in both upper and lower limbs. Tolerance to all three pain modalities was greater in the epidural “blocked” limbs than in the “unblocked” limbs or after intravenous administration, and this difference was sustained after a second injection of narcotic. Sensitivity to carbon dioxide was less depressed by epidural narcotic than by intravenous administration; however, after a second dose of narcotic, depression of CO2 sensitivity by epidural injection was comparable to that produced by intravenous injection. These observations support the hypothesis that epidural narcotics have a segmental action as well as a systematic effect, and that both actions are dose‐dependent.

Exaggerated Spread of Epidural Analgesia in Arteriosclerotic Patients

From time to time reports are published of massive spinal blockade with coma and cardiovascular collapse complicating epidural analgesia. In some cases there seems to be a fairly obvious reason for the accident in the form of direct or circumstantial evidence that the dura was punctured at some stage of the procedure, either before, or during, or after injection of a considerable volume of local anaesthetic into the extradural space (de Saram, 1956 ; Sykes, 1958). In these cases it was assumed that a fair proportion of the solution had found its way into the subarachnoid space through the puncture hole in the dura, causing a massive subarachnoid block, involving the cranial nerves and producing complete deafferentation with resulting loss of consciousness (Gordon-Jones, 1953). However, there have been other cases where no definite reason could be given for the unexpected onset of total spinal blockade (Mostert, 1960). Epidural puncture was technically faultless, and no cerebrospinal fluid or blood could be aspirated from the needle, and yet total spinal blockade and unconsciousness followed the injection of an apparently modest quantity of local anaesthetic solution. Sometimes the accident happened quickly (Stringer, 1954), but often there was a delay of 30 to 40 minutes, or even longer (Morrow, 1959). The published cases seem to have one feature in common. The patients are usually reported as suffering from some degree of arteriosclerotic vascular disease, often associated with diabetes mellitus. During the course of a previous investigation into the spread of epidural analgesia I noticed that arteriosclerotic patients required smaller doses than normal subjects of the same age in order to block a given

Neurological complications following general anaesthesia

A causal relationship between resulting neurological impairment and anaesthetic technique is often assumed after spinal or epidural anaesthesia, despite the rare occurrence of these complications. A postoperative neurological deficit may be closely associated with a general anaesthetic. We present three cases in which neurological sequelae followed recent general anaesthesia: all cases occurred within a period of one year at a single institution. These cases exemplify the difficulty in assuming a causal relationship between neurological deficit and anaesthetic technique.

Rotation of the Epidural Needle: A Caution

be lifesaving in such a circumstance, I question the rationale for recommending the device they describe. First, there are commercially made bougies designed for use in difficult intubations that should be available in every anesthesia department. Second, if a difficult airway is anticipated, one has the time to assemble the necessary equipment beforehand as recommended in the American Society of Anesthesiologists’ difficult airway algorithm (2). It seems to me cavalier to rely on a paper clip and a nasogastric tube to prevent a catastrophe. Third, in a case of unanticipated airway difficulty, one hardly has the time to construct the device, fill a kidney basin full of ice, wait 30 s, then attempt another intubation. Finally, it is unlikely that the recommended device is Food and Drug Administration approved and conforms to the Medical Devices Act of 1990, nor is it likely that a malpractice insurance carrier would cover a lawsuit arising from the improper use of such a device.