A high initial VAS score and sedation afteriv morphine titration are associated with the need for rescue analgesia

PURPOSE: Administration of sc morphine has been recommended two hours after the end of iv morphine titration in the postanesthesia care unit (PACU), but in some cases patients complain of pain earlier than this. We assessed pain after the end of iv morphine titration and studied the characteristics of patients who needed rescue sc morphine. METHODS: Postoperative pain was assessed using the visual analogue scale (VAS; 0 to 100) and the threshold required to administer morphine in the PACU was a score of 30. VAS was measured every 15 min up to two hours after the end of iv morphine titration. Patients were divided into two groups, those who required sc morphine before two hours and those who did not. Data are expressed as mean +/- SD or odds ratio (OR; 95% confidence interval). RESULTS: Four hundred and two patients were analyzed. Mean age was 51 +/- 19 yr, initial VAS 69 +/- 19, and the dose of iv morphine 11.7 +/- 6.6 mg. The number of patients requiring sc morphine within two hours was 84 (21%). These patients had more severe initial postoperative pain (73 +/- 20 vs 68 +/- 19, P < 0.05), and experienced sedation more frequently during morphine titration (45 vs 25%, P < 0.001). Using a multivariate analysis, occurrence of sedation during titration [OR 2.3 (1.4-3.8), P < 0.001] and an initial pain score > or = 60 [OR 1.9 (1.0-3.4), P < 0.05] were significantly associated with the need for rescue sc morphine. CONCLUSION: Sedation during titration and an initial VAS > or = 60 are characteristics of the patients who require rescue (less than two hours) sc morphine after iv morphine titration.     

Auxotypes, plasmid content and serovars of 3 strains of Neisseria gonorrhoeae isolated in Bordeaux in 1955

Penicillinase-producing gonococci are isolated with increasing frequency. Epidemiologic markers, auxotypes, serovars, plasmids have been studied for three strains isolated in Bordeaux, responsible for therapeutic failure. For two of them, the source of contamination could be identified as endemic countries.     

Does the prognosis of cardiac arrest differ in trauma patients?

OBJECTIVE: It is proposed to not resuscitate trauma patients who have a cardiac arrest outside the hospital because they are assumed to have a dismal prognosis. Our aim was to compare the outcome of patients with traumatic or nontraumatic ("medical") out-of-hospital cardiac arrest. DESIGN: Cohort analysis of patients with out-of-hospital cardiac arrest included in the European Epinephrine Study Group's trial comparing high vs. standard doses of epinephrine. SETTING: Nine French university hospitals. PATIENTS: A total of 2,910 patients. INTERVENTIONS: Patients were successively and randomly assigned to receive repeated high doses (5 mg each) or standard doses (1 mg each) of epinephrine at 3-min intervals. MEASUREMENTS AND MAIN RESULTS: Return of spontaneous circulation, survival to hospital admission and discharge, and secondary outcome measures of 1-yr survival and neurologic outcome were recorded. In the trauma group, patients were younger (42 +/- 17 vs. 62 +/- 17 yrs, p < .001), presented with fewer witnessed out-of-hospital cardiac arrests (62.3% vs. 79.7%), and had fewer instances of ventricular fibrillation as the first documented pulseless rhythm (3.4% [95% confidence interval, 1.2-5.5%] vs. 17.3% [15.8-18.7%]). A return of spontaneous circulation was observed in 91 of 268 trauma patients (34.0% [28.3-39.6%]) compared with 797 of 2,642 medical patients (30.2% [28.4-31.9%]), and more trauma patients survived to be admitted to the hospital (29.9% [24.4-35.3%] vs. 23.5% [22.0-25.2%]). However, there was no significant difference between trauma and medical groups at hospital discharge (2.2% [0.5-4.0%] vs. 2.8% [2.1-3.4%]) and 1-yr survival (1.9% [0.3-3.5%] vs. 2.5% [1.9-3.1%]). Among patients who were discharged, a good neurologic status was observed in two trauma patients (33.3% [4.3-77.7%]) and 37 medical patients (50% [38.1-61.9%]). CONCLUSIONS: The survival and neurologic outcome of out-of-hospital cardiac arrest were not different between trauma and medical patients. This result suggests that, under the supervision of senior physicians, active resuscitation after out-of-hospital cardiac arrest is as important in trauma as in medical patients.     

Does taking endurance into account improve the prediction of weaning outcome in mechanically ventilated children?

Introduction  

We conducted the present study to determine whether a combination of the mechanical ventilation weaning predictors proposed by the collective Task Force of the American College of Chest Physicians (TF) and weaning endurance indices enhance prediction of weaning success.     

Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients

IntroductionIn a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity.MethodsWe looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10⁻⁵ digit with no replacement).ResultsA total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality.ConclusionIn a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality.

Trial registration

Clinicaltrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01002482","term_id":"NCT01002482"}}NCT01002482. Registered 26 October 2009.     

Postoperative intravenous morphine titration

Relief of acute pain during the immediate postoperative period is an important task for anaesthetists. Morphine is widely used to control moderate-to-severe postoperative pain and the use of small i.v. boluses of morphine in the post-anaesthesia care unit allows a rapid titration of the dose needed for adequate pain relief. The essential principle of a titration regimen must be to adapt the morphine dose to the pain level. Although morphine would not appear to be the most appropriate choice for achieving rapid pain relief, this is the sole opioid assessed in many studies of immediate postoperative pain management using titration. More than 90% of the patients have pain relief using a protocol of morphine titration and the mean dose required to obtain pain relief is 12 (7) mg, after a median of four boluses. Sedation is frequent during i.v. morphine titration and should be considered as a morphine-related adverse event and not evidence of pain relief. The incidence of ventilatory depression is very low when the criteria to limit the dose of i.v. morphine are enforced. Morphine titration can be used with caution in elderly patients, in children, or in obese patients. In practice, i.v. morphine titration allows the physician to meet the needs of individual patients rapidly and limits the risk of overdose making this method the first step in postoperative pain management.     

Telomerase: a therapeutic target for the third millennium?

Telomerase offers the potential opportunity to control cell proliferation by interfering with a totally new and unique biological process which is cell senescence. The aim of this review is to impartially present the state of the art in telomerase with the pros and the cons of the current scientific situation of this fast-growing and fascinating topic for answering the key question asked by experimental and medical oncologists: Will telomerase be a therapeutic target for the third millenium? The most convincing argument (which is a scientifically documented one) for going ahead with this target is obviously the strong correlation existing between the level and frequency of telomerase expression and the malignant properties of tumors. This has been now largely documented in established tumor cell lines and fresh tumor samples obtained from patients. Noteworthy is the very important difference of telomerase expression between malignant and normal tissues. This difference is much higher than those observed for classical enzymatic targets of chemotherapy such as thymidylate synthetase, dihydrofolate reductase and topoisomerases. If this translates to the clinical situation, telomerase inhibitors might display a good selectivity for tumor cells with a minimal toxicity for normal tissues. The most appealing criticism (which is still purely speculative) is obviously the clinical relevance of inhibiting telomerase in cancer patients. According to the paradigm currently proposed for telomeres and telomerases, it can be predicted that telomerase inhibition will not affect a tumor until its telomeres reach the critical size for entering senescence. This means that during anti-telomerase therapy, the tumor cells will continue grow undergoing 20-30 divisions until the telomeres reach a critical size leading to tumor senescence. Does this make sense, especially in patients with advanced tumors at the beginning of the therapy? Ultimately, the definitive answer to the question will not come from intellectual speculation but from the properties of telomerase inhibitors, first in tumor bearing animals, then finally in cancer patients! Several institutions are very active in the development of telomerase inhibitors. Different stategies are used: direct inhibition of telomerase, interference with telomeres (G quartets), interaction with other proteins involved in the regulation of telomerase and telomeres.     

The expression of the p85α subunit of phosphatidylinositol 3-Kinase is induced by activation of the peroxisome proliferator-activated receptor γ in human adipocytes

Abstract Aims/hypothesis. Thiazolidinediones are new oral antidiabetic drugs that activate the nuclear receptor PPARγ. Our aim was to identify potential target genes of PPARγ in the human adipocyte in order to clarify how thiazolidinediones improve insulin sensitivity. Methods. The effect of BRL 49 653 (Rosiglitazone) on the mRNA expression of insulin receptor, insulin receptor substrate-1, p85α, p110α and p110β subunits of phosphatidylinositol 3-kinase, Glut 4 and hormone sensitive lipase was examined in isolated adipocytes. Target mRNA levels were determined by RT-competitive PCR. Results. The BRL 49 653 (1 μmol/l) increased the mRNA concentrations of p85αPI-3 K (264 ± 46 vs 161 ± 31 amol/μg total RNA, p = 0.003) whithout affecting the expression of the other mRNAs of interest. This effect was dose-dependent (K_0.5 = 5 nmol/l) and was reproduced by a specific activator of RXR, indicating that it was probably mediated by the PPARγ/RXR heterodimer. The BRL 49 653 also increased the amount of p85αPI-3K protein in adipose tissue explants (71 ± 19 %). In addition, BRL 49 653 produced a more than twofold increase in insulin stimulation of phosphatidylinositol 3-kinase activity and significantly enhanced the antilipolytic action of insulin. Conclusion/interpretation. This work demonstrates that the gene of p85αPI-3K is probably a target of PPARγ and that thiazolidinediones can improve insulin action in normal human adipocytes. Although the precise mechanism of action of BRL 49 653 on PI3-Kinase activity is not completely clear, these findings improve our understanding of the insulin-sensitizing effects of the thiazolidinediones, possible drugs for the treatment of Type II (non-insulin-dependent) diabetes mellitus. [Diabetologia (2001) 44: 544–554] Received: 18 May 2000 and in revised form: 2 January 2001     

Interactions of glucagon and free fatty acids with insulin in control of glucose metabolism

To study the interactions of physiological glucagon and free fatty acids (FFA) concentrations with insulin in the control of glucose metabolism, we determined in normal subjects the response of endogenous glucose production (EGP) and glucose utilization (Rd) to a progressive and moderate increase of insulinemia in the presence of glucagon and FFA levels either decreased (somatostatin [SRIF] and insulin infusion, C test) or maintained to normal postabsorptive values isolated (SRIF + insulin + glucagon infusion, G test; SRIF + insulin + Intralipid infusion, IL test) or in association (SRIF + insulin + glucagon + Intralipid infusion, IL + G test). Compared with the C test, maintenance of glucagon level had only small and inconsistent effects on glucose Rd, but induced a shift to the right of the dose-response curve to insulin of EGP (apparent ED50: C test, 10.9 mU.L-1; G test, 15.2 mU.L-1). Intralipid infusion resulted, whether glucagon was substituted or not, in a near total suppression of the insulin-induced increase of glucose Rd (Rd at the end of the tests: C test, 6.13 +/- 0.85 mg.kg-1.min-1; G test, 7.29 +/- 0.87 mg.kg-1.min-1; IL test, 3.30 +/- 0.65 mg.kg-1.min-1; IL + G test, 3.57 +/- 0.42 mg.kg-1.min-1). In the absence of glucagon, substitution Intralipid infusion also antagonized the action of insulin on EGP. However, this effect was no longer apparent when glucagon was replaced (dose-response curve to insulin of EGP during the G and the IL + G test were comparable).(ABSTRACT TRUNCATED AT 250 WORDS)