Enrico M. Camporesi

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.

PATENT FORAMEN OVALE AND DECOMPRESSION SICKNESS IN DIVERS

30 patients with a history of decompression sickness were examined for the presence of patent foramen ovale by bubble contrast, two-dimensional echocardiography and colour flow doppler imaging. With bubble contrast, 11 (37%) of the patients had right-to-left shunting through a patent foramen ovale during spontaneous breathing. 61% of a subset of 18 patients with serious signs and symptoms had shunting. This number was significantly higher than the 5% prevalence seen with the same diagnostic technique in 176 healthy volunteers. The presence of patent foramen ovale seems to be a risk factor for the development of decompression sickness in divers.

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.

Remifentanil update: clinical science and utility.

The anilidopiperidine opioid remifentanil has pharmacodynamic properties similar to all opioids; however, its pharmacokinetic characteristics are unique. Favourable pharmacokinetic properties, minimally altered by extremes of age or renal or hepatic dysfunction, enable easy titration and rapid dissipation of clinical effect of this agent, even after prolonged infusion.Remifentanil is metabolised by esterases that are widespread throughout the plasma, red blood cells, and interstitial tissues, whereas other anilidopiperidine opioids (e.g. fentanyl, alfentanil and sufentanil) depend upon hepatic biotransformation and renal excretion for elimination. Consequently, remifentanil is cleared considerably more rapidly than other anilidopiperidine opioids. In addition, its pKa (the pH at which the drug is 50% ionised) is less than physiological pH; thus, remifentanil circulates primarily in the non-ionised moiety, which quickly penetrates the lipid blood-brain barrier and rapidly equilibrates across the plasma/effect site interface. By virtue of these distinctive pharmacokinetic properties, the context-sensitive half-time (i.e. the time required for the drug’s plasma concentration to decrease by 50% after cessation of an infusion) of remifentanil remains consistently short (3.2 minutes), even following an infusion of long duration (≥8 hours).Remifentanil, a clinically versatile opioid, is useful for intravenous analgesia and sedation in spontaneously breathing patients undergoing painful procedures. Profound analgesia may be achieved with minimal effect on cognitive function. Remifentanil may also provide sedation and analgesia during placement of regional anaesthetic blocks, and in conjunction with topical anaesthesia and airway nerve blocks, it may be useful for blunting reflex responses and facilitating ‘awake’ fibreoptic intubation.Compared with fentanyl and alfentanil in a day-surgery setting, remifentanil supplementation of general anaesthesia may improve intraoperative haemodynamic control. Both emergence time and the incidence of respiratory depression during post-anaesthetic recovery may be reduced. However, outcomes such as home discharge time, post-emergence adverse effect profile, and patient and provider satisfaction are not significantly improved, and the incidence of intraoperative hypotension and bradycardia is greater. In addition, drug acquisition costs for remifentanil are higher and clinicians may need extra time to familiarise themselves with the drug’s unique pharmacokinetics.Ironically, the quick dissipation of opioid analgesic effect following remifentanil discontinuation may be a significant clinical disadvantage. Unless little or no postoperative pain is anticipated, the clinician may wish to treat prospectively using local or regional anaesthesia, non-opioid analgesics, or longer-acting opioid analgesics.

A multicenter evaluation of remifentanil for early postoperative analgesia

We evaluated the use of an infusion of remifentanil to provide postoperative analgesia during recovery from total intravenous anesthesia (TIVA) with remifentanil and propofol.One hundred fifty-seven patients from seven medical centers underwent abdominal, spine, joint replacement, or thoracic surgery. Remifentanil was titrated in an effort to limit pain to 0 or 1 on a 0-3 scale. At the end of the 30-min titration period, 78% of infusion rates were in the range of 0.05 to <or=to0.15 micro g [centered dot] kg-1 [centered dot] min-1, 5% were <0.05 micro g [centered dot] kg (-1) [centered dot] min-1, and 17% were >0.15 micro g [centered dot] kg-1 [centered dot] min-1. Pain scores were 0 or 1 in 64% of patients. Nausea occurred in 35% and emesis in 8% of patients; the peak incidence of nausea followed discontinuation of the remifentanil infusion at the time of administering morphine. Respiratory adverse events (oxygen saturation by pulse oximetry [SpO2] <90% or respiratory rate <12) affected 29% of patients. Apnea occurred in 11 patients (7.0%). There was a large variation in the incidence of respiratory depression between the centers, ranging from 0 to 75%. The explanation for the large variability in respiratory outcome was not evident. (Anesth Analg 1996;83:1292-7).

Half-life of nitric oxide in aqueous solutions with and without haemoglobin

Nitric oxide (NO) has been linked to many regulatory functions in mammalian cells. Studies of NO release are hampered by the short half-life of the molecule. In the blood, NO disappears within seconds because it binds avidly with haemoglobin (Hb). The relationship between Hb concentration and NO disappearance, however, has not been described. In this study we utilized an amperometric NO sensor (WPI, Sarasota, FL) to monitor continuously the disappearance of NO from an aqueous solution when Hb (free or as red blood cells) was added. The calibration and linearity of the NO sensor was checked frequently using a chemical reaction to generate a known concentration of NO. An aliquot of NO solution (prepared from authentic gas) was added to a glass beaker containing 20 ml saline to generate NO concentration of approximately 1200 nM. Under our experimental conditions (PO2 = 40 mmHg), NO concentration fell slowly over 20 min with a half-life of 445 s. However, when haemoglobin was added, NO disappeared rapidly in proportion to Hb concentration. The results suggest that rapid binding of NO to Hb occurs in a 4:1 ratio. The maximum rate constant of NO disappearance due to binding with Hb was 2 x 10(5) M-1 s-1. The 4:1 binding ratio between NO:Hb may be used as a tool to quantitate NO release in some biological assays. The study supports the notion that NO acts as an autocoid because it disappears rapidly in the presence of Hb and is not likely to act as a circulating humoral substance. The NO sensor was useful for monitoring of NO concentration in Hb free solutions, but its response time limits its use in blood.

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.

Mortality reduction in cardiac anesthesia and intensive care: results of the first International Consensus Conference

There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first International Consensus Conference on this topic. The consensus was a continuous international internet‐based process with a final meeting on 28 June 2010 in Milan at the Vita‐Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons, and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting, and ranking. Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic β‐blockade, early aspirin therapy, the use of pre‐operative intra‐aortic balloon counterpulsation, and referral to high‐volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. This International Consensus Conference has identified the non‐surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra‐aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic β‐blockade, early aspirin therapy, and referral to high‐volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.

HYPERBARIC OXYGEN THERAPY FOR RADIATION INDUCED HEMORRHAGIC CYSTITIS

PURPOSE Radiation therapy has been used successfully to treat pelvic malignancy but morbidity from hemorrhagic cystitis remains a major long-term sequela in 1 to 2% of patients. Obliterative endarteritis secondary to ionizing radiation leads to tissue hypoxia and poor healing. Hyperbaric oxygen therapy has been demonstrated to improve angiogenesis and promote healing in radiation injured tissue, including the bladder. We describe the treatment and long-term followup of a cohort of patients treated with hyperbaric oxygen for hemorrhagic cystitis. MATERIALS AND METHODS A total of 17 patients (mean age 62 years) with hemorrhagic cystitis received hyperbaric oxygen following failure of standard treatment modalities. Hyperbaric oxygen was administered on a once daily schedule (mean number of treatments 14) until hematuria resolved. Followup ranged from 9 to 60 months (mean 21). RESULTS Hematuria resolved completely in 11 of 17 patients (64%), 2 had only residual microscopic hematuria, 2 had improvement but died of complications relating to cancer shortly after completion of treatment and 2 had recurrence of gross hematuria. Early application of hyperbaric oxygen was associated with earlier resolution of hemorrhagic cystitis. CONCLUSIONS Radiation induced hemorrhagic cystitis that does not respond to standard regimens can be successfully treated with hyperbaric oxygen. This modality is well tolerated even in patients debilitated by advanced cancer and blood loss. Long-term remission can be achieved in the majority of patients.

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.