Bupivacaine 2.5 mg/ml versus bupivacaine 0.625 mg/ml and sufentanil l microg/ml with or without epinephrine 1 microg/ml for epidural analgesia in labour

We have compared three different methods of epidural analgesia in labour, bupivacaine 2.5 mg/ml (group B), bupivacaine 0.625 mg/ml + sufentanil 1 microg/ml (group BS) and bupivacaine 0.625 mg/ml + sufentanil 1 microg/ml + epinephrine 1 microg/ml (group BSE). One hundred and forty parturients with a singleton fetus with cephalic presentation were randomly allocated to one of the three groups. Group BSE had significantly less pain than groups B and BS. Group B had a significantly higher degree of motor blockade assessed on the Bromage scale. Significantly, more women in group B required urinary bladder catheterization than in the two other groups and they also had significantly less urge to push during active delivery. The incidence of mild pruritus was 18% in group BS and 36% in group BSE. The frequency of instrumental delivery and caesarean section was low (12% and 6.4%, respectively) with no significant differences between the groups. All women were highly satisfied with the method of analgesia and 97% would prefer the same kind of pain alleviation at the next delivery. We conclude that epidural analgesia with low-dose bupivacaine and sufentanil is as good an analgesic method as high-dose bupivacaine. Addition of low-dose epinephrine improves the analgesia.     

Mechanisms of hypercoagulability

Following certain major operative procedures, large amounts of tissue factor may be released from damaged tissues to venous blood. Mechanical and chemical injury to the collecting veins exposes subendothelial procoagulant proteins. This initiates a marked local hypercoagulable process. Subsequently, venous bloodborne procoagulant debris induce a substantial thrombin generation as blood passes the lung capillaries. Thus, the lungs seem to have a central role in the mechanisms of hypercoagulability in high-risk patients. Hypercoagulable blood is squeezed out in the peripheral circulation and may favor thrombosis formation both in central and peripheral vessels. In addition, reduced venous blood flow for several days to weeks after the operation may put these patients at-risk for thromboembolic complications for a long time. Several predisposing genetic and acquired factors associated with thrombophilia have been proposed to contribute to this hypercoagulable process. However, few studies and conflicting results have been reported. The clinical penetrance of the described thrombophilic abnormalities and their contribution to the hypercoagulable process in "high-risk" patients are, at present, unclear. The post-traumatic hypercoagulability seems to be a systemic phenomenon, at least following major orthopedic surgery. Cardiorespiratory and vascular complications play a prominent role as a cause of death and morbidity during and after this kind of surgery.     

CO2 and indomethacin vasoreactivity in patients with head injury

Summary The purpose of this study was to compare the effect of hyper-ventilation and indomethacin on cerebral circulation, metabolism and pressures in patients with acute severe head injury in order to see if indomethacin may act supplementary to hyperventilation. Fourteen severely head injured patients entered the study. Intracranial pressure (ICP), mean arterial blood pressure (MABP) and cerebral perfusion pressure (CPP) were monitored continuously. Within the first four days after the trauma the CO₂ and indomethacin vasoreactivities were studied by measurements of cerebral blood flow (CBF) (Cerebrograph 10a, intravenous¹³³Xe technique) and arterio-venous difference of oxygen (AVdO₂). Ischaemia was evaluated from changes in CBF, saturation of oxygen in the jugular bulb (SvjO₂), lactate and lactate/oxygen index (LOI). Data are presented as medians and ranges, results are significant unless otherwise indicated. Before intervention ICP was well controlled (14.8 (9–24) mmHg) and basic CBF level was 39.1 (21.6–75.0) ml/100 g/min). The arterio-venous oxygen differences were generally decreased (AVdO₂ = 4.3 (1.8–8.1) ml/100 ml) indicating moderate luxury perfusion. Levels of CMRO₂ were decreased (1.54 (0.7–3.2) ml/100 g/min) as well.Duringhyperventilation (APaCO₂ = 0.88 (0.62–1.55) kPa) CBF decreased with 11.8 (–33.4–29.7) %/kPa and ICP decreased with 3.8 (0–10) mmHg. AVdO₂ increased 34.0 (4.0–139.2) %/kPa, MABP was unchanged, CMRO₂ and CPP increased (CPP = 3.9 (–10–20) mmHg). AVD (lactate) and LOI were unchanged. No correlations between CBF responses to hypocapnia and outcomes were observed.An i.v. bolus dose ofindomethacin (30 mg) decreased CBF 14.7 (–16.7–57.4) % and ICP decreased 4.3 (–1–17) mmHg. AVdO₂ increased 27.8 (–40.0–66.7)%, MABP (MABP = 4.9 (–2–21) mmHg) and CPP (CPP = 8.7 (3–29) mmHg) increased while CMRO₂ was unchanged. No changes in AVd (lactate) and LOI indicating cerebral ischaemia were found.Compared to hyperventilation (changes per 1 kPa, at PaCO₂ level = 4.05 kPa) the changes in MABP, CPP and CBF were significantly greater after indomethacin, while the changes in AVdO₂, ICP, SvjO₂, and LOI were of the same order of magnitude.Nocorrelation between relative reactivities to indomethacin and CO₂, evaluated from changes in CBF and AVdO₂, or between the decrease in ICP after the two procedures were found. Thus, some patients reacted to indomethacin but not to hyperventilation, and vice versa.These results suggest that indomethacin and hyperventilation might act independently, or in a complementary fashion in the treatment of patients with severe head injury.     

12% lactate lotion for the treatment of xerosis. A double-blind clinical evaluation

Sixty patients with moderate to severe xerosis participated in a 21-day, randomized, double-blind, contralateral study for efficacy of a specially neutralized 12% lactate lotion compared with a 5% lactic acid lotion and a nonlactated emollient lotion. The severity of xerosis was evaluated on days 0, 7, 14, and 21 during treatment and on days 28 and 35 one and two weeks after treatment was discontinued. All three preparations significantly reduced the severity scores of xerosis. During the "regression" period after treatment was discontinued, patients receiving 12% lactate lotion, compared with those treated with nonlactated emollient lotion, had had significantly greater reductions in the severity scores of xerosis for the lateral calf area at days 28 and 35 and for total severity scores (combined mean differences for lateral, medial, and pretibial areas) at day 35. Compared with 5% lactic acid lotion, the 12% lactate lotion provided significantly greater reductions for total severity scores at days 28 and 35.     

Enantioselective hydroxylation of nortriptyline in human liver microsomes, intestinal homogenate, and patients treated with nortriptyline

The enantioselectivity of hydroxylation of nortriptyline (NT) to E-10-hydroxynortriptyline (E-10-OH-NT) was studied in human liver microsomes, intestinal homogenate, and patients treated with NT. The rate of formation of (-)-E-10-OH-NT was higher than that of (+)-E-10-OH-NT both in the liver microsomes and in the intestinal homogenate. Quinidine, a prototype competitive inhibitor of the cytochrome P450IID6 ("debrisoquin hydroxylase"), inhibited the formation of (-)-E-10-OH-NT in a concentration-dependent manner in liver microsomes, while the formation of (+)-E-10-OH-NT was hardly affected. This indicates that P450IID6 catalyzes the hydroxylation of NT in a highly enantioselective manner to (-)-E-10-OH-NT in the liver. Another P450 isozyme besides IID6 seems to be responsible for the formation of the (+)-enantiomer in the liver. In intestinal homogenate, the formation of both enantiomers of E-10-OH-NT was inhibited to about the same extent by quinidine, the maximum inhibition being much less than in the liver. In the urine of six patients treated with NT, the (-)-enantiomer accounted for 91 +/- 2% of the unconjugated E-10-OH-NT, and for 78 +/- 6% of the glucuronide conjugates. The study shows that NT is hydroxylated in a highly enantioselective way, probably catalyzed by the polymorphic P450IID6, to (-)-E-10-OH-NT both in vitro in human liver as well as in vivo in patients treated with the drug.     

Multicenter phase II study of Nordic fluorouracil and folinic acid bolus schedule combined with oxaliplatin as first-line treatment of metastatic colorectal cancer.

PURPOSE: This Nordic multicenter phase II study evaluated the efficacy and safety of oxaliplatin combined with the Nordic bolus schedule of fluorouracil (FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer. PATIENTS AND METHODS: Eighty-five patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1, followed by a 3-minute bolus injection with FU 500 mg/m(2) and, 30 minutes later, by a bolus injection with FA 60 mg/m(2) every second week. The same doses of FU and FA were also given on day 2. RESULTS: Fifty-one of 82 assessable patients achieved a complete (n = 4) or partial (n = 47) response, leading to a response rate of 62% (95% CI, 52% to 72%). Nineteen patients showed stable disease, and 12 patients had progressive disease. Thirty-eight of the 51 responses were radiologically confirmed 8 weeks later (confirmed response rate, 46%; 95% CI, 36% to 58%). The estimated median time to progression was 7.0 months (95% CI, 6.3 to 7.7 months), and the median overall survival was 16.1 months (95% CI, 12.7 to 19.6 months) in the intent-to-treat population. Neutropenia was the main adverse event, with grade 3 to 4 toxicity in 58% of patients. Febrile neutropenia developed in seven patients. Nonhematologic toxicity consisted mainly of neuropathy (grade 3 in 11 patients and grade 2 in another 27 patients). CONCLUSION: Oxaliplatin combined with the bolus Nordic schedule of FU+FA (Nordic FLOX) is a well-tolerated, effective, and feasible bolus schedule as first-line treatment of metastatic colorectal cancer that yields comparable results compared with more complex schedules.     

Fibrosarcoma in Children: A Rare Tumour with Long-Term Survival even with Advanced Disease A Report of 3 Cases

Fibrosarcoma is a rare tumour in children. The potential of malignancy has been questioned. We present three cases of fibrosarcoma in children. The follow-up periods range from 10 to 37 years. The first patient had pulmonary metastases at the time of diagnosis in 1958. The primary tumour in fossa ischio-rectalis was resected in 1960. Lung metastases were resected in 1960 and 1989. Radiotherapy was given in 1992. He is still alive with metastases 37 years after the first manifestation of disease. The second patient had a primary tumour and several local recurrences in the mandible. He is alive without evidence of disease 4 years after resection of pulmonary metastases and 21 years after resection of the primary tumour. The third patient has no signs of recurrence or metastasic spread 10 years after a wide excision of subcutanous tumours of the left upper arm. The cases demonstrate a special tumour-entity of low-grade malignancy, which show a good prognosis and a wide spectrum of biological behaviour.     

The effect of systemic lidocaine on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers

Although effective in neuropathic pain, the efficacy of systemic lidocaine in non-neuropathic pain remains uncertain. We investigated the analgesic effect of systemic lidocaine on the heat/capsaicin sensitization model of experimental pain in 24 volunteers. Sensitization was produced by heating the skin to 45 degrees C for 5 min, followed by a 30-min application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin. Subjects received IV lidocaine (bolus 2 mg/kg, then infusion 3 mg. kg. h), or saline for 85 min. Areas of secondary hyperalgesia, heat pain detection thresholds, and painfulness of stimulation with 45 degrees C for 1 min (long thermal stimulation) were quantified. Systemic lidocaine reduced the area of secondary hyperalgesia to brush, but not to von Frey hair stimulation. Lidocaine did not alter heat pain detection thresholds or painfulness of long thermal stimulation in normal skin. We conclude that, at infusion rates in the low- to mid-antiarrhythmic range, lidocaine has no effect on acute nociceptive pain but does have a limited and selective effect on secondary hyperalgesia. Implications: The efficacy of systemic lidocaine in nonneuropathic pain remains uncertain. This study investigates the effect of systemic lidocaine on experimental-induced hyperalgesia in 25 volunteers. Hyperalgesia was induced by using an experimental pain model that uses heat and capsaicin in combination. Systemic lidocaine showed a selective effect on secondary hyperalgesia.