Nosocomial urinary tract infection (NUTI) is the second most frequent nosocomial infection in ICU. Decreasing the infectious risk can only be achieved by targeting indications, and duration of catheterizing. Inserting a urinary catheter is often performed under aseptic surgical conditions even though the efficacy of this procedure has not been demonstrated in ICU. Several studies have reported that using catheters coated with antiseptics or antibiotics decreases the frequency of UTIs, but induces overcosts. The closed system remains a reference technique. Basic body hygiene seems to be efficient enough for daily care. To conclude, the prevention of UTIs is linked to the quality of care, especially nursing care, and for some a marker of the quality of care. (C) 2003 Editions scientifiques et medicales Elsevier SAS. Tous droits reserves.

The topical administration of ointments containing salicylic acid to large areas of impaired skin can result in systemic salicylate intoxication [1,2], with a fatal result in some cases [3]. The symptoms are usually correlated with drug intake or serum salicylic acid concentrations [4]. We report the case of an HIV-infected patient who presented with symptoms of salicylate intoxication after the topical administration of salicylic ointment, despite moderate plasma levels of salicylates. Case report This 31-year-old patient with advanced HIV infection (CD4 cell count 64 cells/mm3; plasma HIV-1-RNA load 50 000 copies/ml; body weight 38 kg) was hospitalized for a worsening of severe psoriasis in September 2001. The patient was lost to follow-up for his HIV infection. Psoriasis with articular complications was treated with methotrexate until January 2001. In our unit, he received 30% salicylic ointment, applied to the back and the four limbs. Two days after continuous application of salicylic ointment, the patient was found in a coma, with no clinical orientation. The laboratory tests showed an oxygen saturation of 84% that increased to 91% after oxygen. On admission to the intensive care unit, his clinical condition was unchanged; arterial blood gas analysis revealed a metabolic acidosis, hypoxia and hypocapnia. Serum electrolyte values were potassium 3.3 mmol/l, bicarbonate 6.3 mmol/l, with an anion gap of 19.6. The serum glucose concentration was initially 5.7 mmol/l, but rapidly increased. C-reactive protein was 297 mg/l. Blood pressure was 120/70 mmHg; pulse was 120 beats/min; respiratory rate was 35 breaths/min; oxygen saturation was 96% on oxygen; and Glasgow score was 13. Electrocardiogram showed a sinusal rhythm. The chest X-ray showed bilateral alveolar-interstitial syndrome, which normalized within 3 days. Moreover, the suspected aetiologies (infectious or cardiac) were not confirmed by the laboratory tests. Ointment with salicylic acid was then suspected to be the cause of the metabolic acidosis. Serum salicylate levels were found to be as high as 309 mg/l and 260 mg/l a few hours later, paralleling clinical improvement, and supporting the diagnosis. Symptomatic treatment with oxygen, a close monitoring of biological data, and intensive hydration were the only treatments. All variables rapidly returned to normal, and the patient was able to return to a conventional medical unit, in which antiretroviral treatment was initiated. Discussion Severe salicylate intoxication is associated with clinical symptoms such as disturbed consciousness, coma, hyperpyrexia, Kussmaul–Kien dyspnoea, and biological disturbances such as hyperglycaemia followed by hypoglycaemia, hypernatremia but also hyponatremia, hypokaliemia, and metabolic acidosis [4]. Many of these clinical and laboratory findings were present in our patient (Table 1).Table 1: Summary of laboratory results for patient reported in case history. Our patient had been treated with a high dose of salicylic acid, applied to extensive diseased skin areas. He presented with symptoms of severe salicylate intoxication, despite plasma levels (309 mg/l) that were found to be minimally above the considered superior therapeutic limit (300 mg/l). According to previous published reports, symptoms are not severe when salicylemia is less than 500 mg/l [4]. Many hypotheses may explain the severity of the symptoms observed in our patient despite the moderate salicylate serum levels observed. Our patient presented with advanced HIV infection, which is associated with a systemic glutathione deficiency [5]. A deficiency in glutathione in HIV patients leads to increased oxidative stress, and the production of pro-inflammatory cytokines (IL-1, IL-6, and TNF-α), which stimulate HIV replication [5]. Moreover, our patient had a very low body weight, and cachexia. In 10 AIDS cachectic patients, a significant increase in pro-inflammatory cytokines, and a decrease in regulatory cytokines (IL-12) were observed [6]. The pathophysiology of salicylate intoxication has been well described [4]. Salicylates have been shown to inhibit oxidative phosphorylation and mitochondrial respiration, which decreases the cells’ ability to produce ATP [4]. This inhibition leads to increased amounts of pyruvate, lactate and ketones, which induce hyperthermia, glycogenolysis, and metabolic acidosis [4]. Paradoxically, acetylsalicylate can create a systemic inflammatory response syndrome (SIRS) when administered at toxic amounts, or when given therapeutically to children with mild viral infections [7]. This syndrome is caused by the release of pro-inflammatory cytokines. This may well be the first rational explanation of the paradoxically pro-inflammatory effects of salicylates [8]. It could also explain the ability of salicylates to increase the cytokine-induced generation of inducible nitric oxide synthase and nitric oxide in vitro, when IL-1β is present [8]. SIRS is defined as the presence of several symptoms such as disturbances of heart rate or tachypnea [9]. Acute lung injury and encephalopathy may also be observed [9]. Major changes in carbohydrate metabolism have been reported. The common final result is hyperglycaemia. Lactate levels may rise moderately [9]. An increase of lactic acid and hyperglycaemia were also observed in our patient, although salicylate intoxication is almost always associated with hypoglycaemia. Moreover, the pulmonary clinical picture observed in our patient is compatible with the adult respiratory distress syndrome described in SIRS. What we observed in our patient could be compared with disturbances of β-oxidation or the release of cytokine-induced nitric oxide reported in young patients suffering from Reye's syndrome [10]. Our patient presented with symptoms of acute salicylate toxicity and SIRS. We speculate that the release of pro-inflammatory cytokines by HIV, especially in a cachectic patient, associated with the use of salicylate, may explain the severe symptoms observed, despite lower plasma levels than those observed in patients without viral infection. As a result of the severity of the symptoms observed in this case, we would recommend that the use of salicylate in HIV patients should be closely monitored in naive- and especially nucleoside reverse transcriptase inhibitor-treated patients. Hélène Peyrierea Nicolas Balmesb Isabelle Rouanetc Jean-Marc Mauboussinc Dominique Hillaire-Buysa Charles Arichb Jean-Pierre Blayaca Denis Vincentc Acknowledgements The authors would like to acknowledge the help of Professor G. Halpern in the translation.

OBJECTIVE:To determine the efficacy and safety of using natural platelet-activating factor receptor antagonist (PAFra), BN 52021, to treat patients with severe Gram-negative bacterial sepsis.DESIGN:A prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial.SETTING:Fifty-nine academic medical center intensive care units in Europe.PATIENTS:Six hundred nine patients with severe sepsis, suspected to be related to Gram-negative bacterial infection, who received PAFra or placebo.INTERVENTIONS:Patients were randomized to receive either a dose of PAFra (120 mg iv) every 12 hrs over a 4-day period or placebo over a 4-day period.MEASUREMENTS AND MAIN RESULTS:The patients were well matched at study entry for severity of illness and for risk factors known to influence the outcome of sepsis. Among all randomized patients, the 28-day, all-cause mortality rate was 49% (152/308) in the placebo group, and 47% (140/300) in the PAFra group (p=.50). When analyzed on the basis of the previously defined target population, the 28-day, all-cause mortality rate was 50% (115/232) in the placebo group and 44% (94/212) in the PAFra group, yielding a 12% reduction in mortality rate (p=.29). In patients with documented infection involving other organisms, there was no difference between treated and placebo groups. When the outcomes of organ dysfunctions were examined in the overall population and in the documented Gram-negative bacterial infection population, the number of patients who resolved hepatic dysfunction tended to be higher in the treated group than in the placebo group (p=.06). The number of adverse events reported were not different between the two groups.CONCLUSIONS:A 4-day administration of the studied PAFra (BN 52021) failed to demonstrate a statistically significant reduction in the mortality rate of patients with severe sepsis suspected to be related to Gram-negative bacterial infection. If PAFra treatment has any therapeutic activity in severe Gram-negative bacterial sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial.

Évaluer l'impact sur les coûts d'un protocole de prescription des solutés de remplissage et d'alimentation artificielle.Étude comparative, avant et après introduction du protocole.L'étude a porté sur 555 patients admis en réanimation, répartis en deux groupes, avant et après protocole, homogènes (nombre de malades, type de pathologie, âge, IGS, durée de séjour, points oméga total/j, incidence des infections nosocomiales, mortalité).En février 1995, un protocole écrit, fondé sur les données de la littérature, a défini de façon restrictive les indications des solutés de remplissage (hydroxyéthylamidon et albumine humaine prescrits uniquement pour des indications reconnues) et de l'alimentation parentérale (au profit de l'alimentation entérale de première intention). Les coûts ont été comparés sur deux périodes de 6 mois : avant (août 1994 à janvier 1995) et après protocole (février à juillet 1995).Après l'introduction du protocole, les prescriptions d'albumine ont diminué d'un tiers, celles d'hydroxyéthylamidon de plus de la moitié, alors que celles de gélatines et de cristalloïdes ont été plus importantes. Une économie de 15 000 francs (20 % sur ce poste budgétaire) a été réalisée. La limitation des indications de la nutrition parentérale au profit de la voie entérale précoce a généré une économie de 56 000 francs (31 % sur ce poste budgétaire).Ce protocole de prescription a entraîné une économie de 9 % sur le budget pharmacie permettant d'augmenter l'efficience du service.To assess the economic impact of a prescribing protocol for IV fluid therapy and artificial nutrition.Comparative study, before and during use of the protocol.The study included 555 ICU patients allocated into two groups, before and after starting with the protocol. The groups were comparable for number, pathologies, age, severity score, duration of ICU stay, incidence of nosocomial infections, mortality rate.In February 1995, a written literature-based prescribing protocol for fluid therapy (hydroxyethylstarch and albumin), and artificial nutrition (enteral nutrition as first-line therapy) was devised. A cost analysis was made for two 6-month periods: before (August 1994 to January 1995) and after start of protocol (February to July 1995).The prescription of albumin and hydroxyethylstarch decreased (by 33 and 58% respectively), whereas administration of Ringer lactate and gelatine solutes increased simultaneously. This induced a cost saving of 15,000 FF (a 20% decrease in cost). The reduction of parenteral nutrition in favour of early enteral nutrition induced a cost saving of 56,000 FF (31% decrease in cost).Our prescribing protocol generated a cost saving of 9% of the pharmaceutical budget and decreased the costbenefit ratio of our ICU.

A 32-year-old pregnant woman developed meningococcemia associated purpura fulminans and quickly improved with therapy. After this disease C4b-Binding Protein (C4bBP) plasma levels remained very low while protein S activity was in the normal range. Familial investigation proved a hereditary C4bBP deficiency. This observation points out the role of the protein C-protein S system during acquired purpura fulminans.

The authors report two cases of arteriovenous fistula due to spontaneous rupture of an aortic or iliac aneurysm into the iliocaval venous axis. This is a rare complication of atheromatous aneurysm (less than 4 % of ruptured aneurysms), often difficult to diagnose as the clinical presentation may be obscure. Although aortography is the reference diagnostic investigation, color Doppler ultrasonography enabled visualisation of the arteriovenous communication and provided an accurate diagnosis in one recent case. Treatment of these aortocaval fistulae is always surgical. The prognosis and immediate operative mortality depend mainly on the presence of an associated retroperitoneal rupture.

The authors report two cases of arteriovenous fistula due to spontaneous rupture of an aortic or iliac aneurysm into the iliocaval venous axis. This is a rare complication of atheromatous aneurysm (less than 4% of ruptured aneurysms), often difficult to diagnose as the clinical presentation may be obscure. Although aortography is the reference diagnostic investigation, color Doppler ultrasonography enabled visualisation of the arteriovenous communication and provided an accurate diagnosis in one recent case. Treatment of these aortocaval fistulae is always surgical. The prognosis and immediate operative mortality depend mainly on the presence of an associated retroperitoneal rupture.

Serial studies of the plasma protein C-protein S System were performed during the clinical course of a pregnant woman with meningococcaemia who recovered under therapy. The patient had limited purpura fulminans skin lesions and hereditary C4b-binding protein deficiency was suspected. This diagnosis was confirmed in the patient 1 year after delivery and also by family studies. During the meningococcaemia, an initial mild and transient acquired protein C deficiency was seen but no protein S deficiency was observed despite consumption of the latter protein. As C4b-binding protein partial deficiency is associated with high free protein S and protein S activity, this may have protected against acquired protein S deficiency during meningococcaemia.

Serial studies of the plasma protein C-protein S system were performed during the clinical course of a pregnant woman with meningococcaemia who recovered under therapy. The patient had limited purpura fulminans skin lesions and hereditary C4b-binding protein deficiency was suspected. This diagnosis was confirmed in the patient 1 year after delivery and also by family studies. During the meningococcaemia, an initial mild and transient acquired protein C deficiency was seen but no protein S deficiency was observed despite consumption of the latter protein. As C4b-binding protein partial deficiency is associated with high free protein S and protein S activity, this may have protected against acquired protein S deficiency during meningococcaemia.

Respiratory alkalosis, produced by mechanical ventilation, has been identified as a cause of hypoxemia, which improves when PaCO2 is normalized or increased. Moreover, moderate hypercapnia has been suggested for the treatment of acute respiratory failure (ARF) by the results observed in experimental animals. To correct the situation of hyperventilation one option therapeutic is the addition of dead space (VD). Whereas pulmonary disease that impairs the lung s capability to oxygenate the arterial blood can be evaluated with the utilization of oxygen tension-based indices such as: F(A-a)02, PaO2/PA02, Pa02/FiO2, and Respiratory Index R.I.= P(A-a)O2/PaO2, or oxygen content-based indices such as: Estimated Shunt (Est Bunt). To determine the effects of hypo, normo and hypercapnia on the variations in arterial oxygenation and their indices in critical patients with acute respiratory failure (ARF) receiving mechanical ventilation. 15 ARF patients, prospective and randomized, intubated and mechanically ventilated, were studied within the first 48 hours of evolution. Three stages warp delimited: I) 30 min after the beginning of anaesthesia; II) 30 min after adding 30 cm of dead space (VD); III) 30 min after replacing the previous VD with VD of 60 cm. Ventilation parameters and FiO2 were kept stable. Stage I was characterized by respiratory alkalosis and stage II by normal acid-base balance with an increase in Pa02 (p<0.01) and a decrease in intrapulmonary shunt (Qsp/et) (p<0.001); the indices alveolar to arterial oxygen tension gradient EP(A-a)02], respiratory index (R.I.) and estimated shunt (Est Shunt) also decreased significantly, whereas arterial to alveolar oxygen tension ratio (Pa02/FA02) and arterial oxygen tension to inspired oxygen fraction ratio (Pa02/FiO2) increased significantly. In stage III there was pure hypercapnic acidosis, with decreases in PA02 (p<0.001), P14-a1O2 (p<O.01) and R.I. (p<0.05), while Pa02, Qsp/Qt, Est Shunt, Pa02/PAO2 and Pa02/FiO2 remained stable with respect to the previous situation. Conclupion. It is suggested that " qualitativeli" changes or/and "extra-alveolar" modifications due to localo' regional pulmonary perfusion are responsible for the observed variations. The indices P(A-a)02 and R.I. do not allow us to differentiate the causes of arterial h.ypcxemia in the presence of hypercapnia. P419

In mechanically ventilated patients (pts), nosocomial pneumonia (NP) often originates from oropharyngeal (0) and gastric (C) flora. The main bacterial reservoir is not clearly defined. The goal of this study was to establish a relationship between quantitative bacterial culture of salivary (S) and (G) samples and the occurence of NP. We conducted a preliminary prospective survey in 46 ICU medical (n = 33) and surgical In = 13) pts, ventilated on entry, with an ICU stay over 48 H. Gastric pH, S and G samples were studied on entry and twice weekly by quantitative cultures (>100 cfu/ml) on appropriate media for Gram negative bacilli, S aureus, Enterococcus and yeasts. Bacteria were compared by molecular typing (pulsed field gel electrophoresis). Nosocomial pneumonia was strictly defined by the association of clinical, radiologic and microbiologic quantitative criteria. To identify risk factors for NP, baseline characteristics of the infected pts were compared with those of controls, as well as previous occurrence of S or G colonization (> 10 6 cfu/ml), by score test, using Cox's model. Relative risk (RR) of developing NP was estimated by exponentiation of each Cox's regression coefficient. 11 NP (5 Acinetobacter sp., 3 Enterobacter sp., 1 S. aureus, 1 Klebsiella pneumoniae, 1 Enterococcus) were observed. The NP rate wäs estimated at 9 p. cent at day 5, and 29 p. cent at day 10. Pts with NP were more likely than controls to have immunodeficiency (p = .04) and longer previous hospitalization (p = .05), but immunodeficiency was the only independent risk factor for NP selected by the multivariate analysis (RR = 3.6, p = .04). Otherwise, no influence was observed on the risk of developing NP by G colonization (RR = .9, p = .83), while influence, although not significant, was exerted by S colonization (RR = 2, p = .40). Moreover, such influence strongly appeared on the risk of developing Acinetobacter sp. NP: previous salivary culture for Acinetobacter sp. > 106 cfu/ml increased about 14-fold the risk of developing Acinetobacter sp. NP (p = .006).