Laurence Mier

Continuous versus Intermittent Infusion of Vancomycin in Severe Staphylococcal Infections: Prospective Multicenter Randomized Study

ABSTRACT A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 ± 31 versus 51 ± 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 ± 2.2 versus 11.8 ± 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC24h) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg2/liter2/h2[P = 0.026] and 414 versus 818 g2[P = 0.057], respectively). The 10-day treatment cost per patient was

Is penicillin G an adequate initial treatment for aspiration pneumonia ? A prospective evaluation using a protected specimen brush and quantitative cultures

454 ± 137 in the IIV group and was 23% lower in the CIV group (

Safety, efficacy, and cost-effectiveness of mechanical ventilation with humidifying filters changed every 48 hours: a prospective, randomized study.

321 ± 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.

Use of Inhaled Nitric Oxide To Reverse Flow through a Patent Foramen Ovale during Pulmonary Embolism

ObjectiveTo evaluate the bacteriology of early aspiration pneumonia using a protected specimen brush and quantitative culture techniques, and whether penicillin G is adequate as initial treatment pending culture results.Patients and methods52 patients (of which 45 required mechanical ventilation) meeting usual clinical criteria for aspiration pneumonia were prospectively included. On admission, patients were given intravenous penicillin G and a protected specimen brush was performed ≤48 h after.ResultsCultures of the brush were negative (<103 CFU/ml) in 33 patients (1 had blood cultures positive withS. pneumoniae) and positive (≥103 CFU/ml) forS. pneumoniae in 2 patients. Seventeen patients had a positive culture (≥103 CFU/ml) for at least one penicillin G resistant microorganism, with a total of 20 organisms (S. aureus: 6;H. influenzae: 2;Enterobacteriaceae: 8;P. aeruginosa: 3;C. albicans: 1). In 4 of these patients, a penicillin-sensitive pathogen was also recovered in significant concentrations (S. pneumoniae: 2;Streptococcus sp.: 2). These 17 patients with a resistant pathogen did not differ from the 35 other patients with respect to need for ventilatory support and mortality rate. By contrast, they were older (61.1±21.9 vs 42.9±18.8 years;p<0.005) and required longer mechanical ventilation (6.1±4.6 vs. 3.5±2.7 days;p<0.03) and hospitalization (11.2±8.8 vs. 6.7±4.7 days;p<0.02). Of 17 patients 12 with penicillin G resistant organisms versus 0/35 without, were in-hospital patients and/or had a digestive disorder (p<0.001).ConclusionThe broad range of offending organisms seen in early aspiration pneumonia precludes use of any single empiric regimen, making protected specimen brush mandatory in many patients. Nevertheless, the involvement ofS. pneumoniae in a notable proportion of our patients suggests that routine penicillin prophylaxis after early aspiration (at least in most patients with community-acquired aspiration) is warranted given the potential severity of pneumococcal sepsis in such patients.

Measurement of cardiac output by transesophageal echocardiography in mechanically ventilated patients

Objective: To determine whether three hydrophobic and hygroscopic heat and moisture exchangers (HMEs) retain their heating and humidifying properties (assessed by psychrometric measurements of absolute humidity, relative humidity, and tracheal temperature) for 48 hrs without any drop in their bacteriologic efficiency. Design: Prospective randomized clinical trial. Patients: Sixty‐one consecutive unselected mechanically ventilated intensive care unit patients. Interventions: Patients were randomly allocated to one of the three HMEs studied (Hygrobac‐Dar from Mallinckrodt, n = 21; Humid‐Vent from Gibeck, n = 20; and Clear‐Thermal from Intersurgical, n = 20). Measurements and Main Results: Hygrometric parameters were measured by psychrometry after 3, 24, and 48 hrs of use. Peak airway pressure was recorded every 6 hrs and averaged over 24 hrs. Bacterial colonization of both patients and circuits was studied. Patients in all three groups were similar in terms of age, indications for, and overall duration of mechanical ventilation. Tracheal tube occlusion never occurred. Hygrometric data included 371 measurements whereas bacteriologic data included >700 samples and cultures. The Hygrobac‐Dar HMEs gave a significantly higher absolute humidity whatever the time of measurement (3, 24, or 48 hrs) than the other two HMEs (p < .001). The Clear‐Thermal HMEs gave the poorest hygrometric parameters (p < .01); five of them were replaced prematurely (24 hrs) because the absolute humidity was <25 mg H2O/L. This did not occur for the other HMEs. Mean peak airway pressures were identical in the three groups. The bacterial colonizations of both patient and circuit were similar (and negligible for circuits) for all three groups. Conclusion: Some HMEs may be used safely for 48 hrs without change. However, this does not pertain to every brand of HME. Objective in vivo evaluation of their humidifying performances is decisive before extending their duration of use.

Mechanical ventilation with heated humidifiers or heat and moisture exchangers: effects on patient colonization and incidence of nosocomial pneumonia.

The presence of a patent foramen ovale during pulmonary embolism may promote right-to-left shunting when right atrial pressure exceeds that in the left atrium. This may cause severe hypoxemia and paradoxical embolism [1]. The diagnosis of this complication has benefited from contrast transesophageal echocardiography [2]. Invasive procedures, such as transcatheter or surgical closure, are usually required [3] but may not be easily done in unstable patients. Reversing the right-to-left atrial pressure gradient may promote closure of the patent foramen ovale. We report an example of this reversal using inhaled nitric oxide, a potent pulmonary vasodilator [4-7]. Case Report A 74-year-old woman was admitted to our intensive care unit with deep coma and acute respiratory failure requiring mechanical ventilation. A complete right bundle-branch block was seen on the electrocardiogram. Despite clear lung fields on the chest radiograph, the pulmonary angiographic results showed a massive embolism (the Miller index [8], 23/34). A continuous intravenous infusion of heparin was immediately started. A cerebral computed tomographic scan showed several cerebral infarctions in the vertebrobasilar system. A patent foramen ovale was suspected, and transesophageal echocardiography using an Aloka SSD-870 device Aloka, Tokyo, Japan with a 5-MHz monoplane probe showed an atrial septal aneurysm (Figure 1, top left). A right-to-left shunt through a patent foramen ovale was observed using contrast by injecting gelatin into the right atrium; this shunt appeared as echoes massively moving from the right atrium to the left atrium (Figure 1, top right). Simultaneous hemodynamic measurements obtained with a fast-response thermistor Swan-Ganz catheter (Baxter, Irvine, California) and with transesophageal echocardiography were done while the patient was mechanically ventilated with a fraction of inspired oxygen (Fio 2) of 0.6. Figure 1. Transesophageal echocardiography in the four-chamber plane. Top left. arrows LA Top right RA LV Bottom left The presence of a patent foramen ovale was considered life-threatening in this patient. We therefore decided to administer inhaled nitric oxide in the hope of promoting closure of the patent foramen ovale, following advice from two outside consultants (senior cardiologist and pulmonologist) not involved in the treatment of the patient. This treatment was explained to her family and they agreed that we could try the procedure. Inhalation of 25 parts per million of nitric oxide (Compagnie Francaise de Produits Oxygenes, Paris, France) completely abolished the passage of microbubbles from the right to the left atrium (Figure 1, bottom left) and dramatically improved hemodynamic values and gas exchange. Although the mean systemic arterial pressure remained unchanged (115 mm Hg with vasopressor agents), the mean pulmonary arterial pressure decreased markedly (41 to 36 mm Hg). The right atrial pressure (12 to 13 mm Hg) increased less than the left atrial pressure (which was inferred from the pulmonary artery occlusive pressure [11 to 14 mm Hg]); the net effect was a reversal of the right-to-left atrial pressure gradient. The mixed venous partial pressure of oxygen increased from 34 to 41 mm Hg, whereas the venous admixture decreased from 31% to 14%. The Pao 2 increased from 61 to 133 mm Hg. Surgical or transcatheter closure of this patent foramen ovale was not considered feasible because of the patients poor neurologic status. The patient was therefore maintained on prolonged nitric oxide administration. Serial echographic examinations showed persistent closure of the patent foramen ovale; the patients condition deteriorated, and brain death occurred on day four. Permission for autopsy was denied. Discussion To our knowledge, this is the first case of functional closure of a patent foramen ovale using inhaled nitric oxide or using nitric oxide during pulmonary embolism. The prevalence of a patent foramen ovale, as shown by contrast transesophageal echocardiography, is 20% to 30% in unselected patients [9]. Coexistence of an atrial septal aneurysm, as in our patient, seems to occur more frequently in patients with stroke [9]. A foramen ovale may open during massive pulmonary embolism when the right atrial pressure increases above the left atrial pressure. This creates a right-to-left shunt that worsens hypoxemia and favors paradoxical embolism. Early recognition and treatment of this complication may be life-saving. However, the diagnosis of pulmonary embolism is difficult. In our patient, for example, the chest radiograph was normal despite the presence of massive pulmonary embolism. Diagnosis of the patent foramen ovale was facilitated by the availability of contrast echocardiography, which can be done accurately at the bedside [10]. Surgical or transcatheter closure has been advocated [3] but may not be easily done in unstable patients. In pulmonary embolism, an increase of pulmonary vascular resistance is the consequence of anatomic obstruction and pulmonary arterial constriction [11]; therefore, we reasoned that a decrease of the latter factor using inhaled nitric oxide might abolish the right-to-left shunting. Indeed, nitric oxide is an endothelium-derived relaxing factor with important modulating effects on vascular smooth-muscle tone; nitric oxide can also decrease pulmonary vascular resistance in various forms of pulmonary hypertension [4-7]. Nitric oxide may also increase arterial oxygenation by improving ventilation-perfusion matching without producing systemic vasodilatation [7]; thus, we also administered nitric oxide to our patient in the hope of improving the ventilation-to-perfusion mismatch, which can contribute to altered gas exchange during pulmonary embolism [11]. In our patient, inhalation of nitric oxide markedly decreased the pulmonary artery pressure. This decrease occurred despite a probable increase in cardiac output as shown by a substantial increase in the mixed venous partial pressure of oxygen; this suggested that pulmonary vascular resistance had decreased. The loss of an indicator across the shunt prevented accurate computation of the cardiac output and derived variables. As a probable consequence of improved pulmonary hemodynamic values, we observed a reversal of the pressure gradient between the right and left atria. This was associated with a disappearance of right-to-left shunting on contrast studies. The marked increase in Pao 2 after nitric oxide inhalation was because of an increase in the mixed venous partial pressure of oxygen and a decrease of the venous admixture. The latter may be ascribed to suppression of intracardiac shunting and possibly improvement in the ventilation-perfusion distribution [7, 11]. This report suggests that using nitric oxide may be beneficial pending the decision to do surgical or transcatheter closure of the patent foramen ovale in patients with massive pulmonary embolism. However, additional studies are necessary to determine its utility during severe pulmonary embolism with or without patent foramen ovale.

Changing heat and moisture exchangers every 48 hours rather than 24 hours does not affect their efficacy and the incidence of nosocomial pneumonia.

Objective: The determination of basal cardiac output (CO) and of its variations during different therapeutic interventions liable to increase or decrease it in mechanically ventilated patients using transesophageal echocardiography (TEE). Design: To compare CO measurements simultaneously obtained by transmitral single-plane TEE and thermodilution. Setting: Medical intensive care unit. Patients: Twenty-two consecutive mechanically ventilated patients hospitalized for various medical conditions were included. Interventions: The comparisons between transmitral single-plane TEE and thermodilution measurements were made at baseline and after different therapeutic interventions affecting CO (fluids or dobutamine infusion or positive end-expiratory pressure titration). Measurements: Seventy-four measurements were obtained. Cardiac output using TEE was the product of the mitral valve area, the time-velocity integral of flow at the same site and the heart rate. Results: A significant correlation was observed between thermodilution and TEE measurements of CO (n = 74, r = 0.78, p < 0.001) despite wide limits of agreement (mean ± 2SD = –0.3 ± 3.1 l/min). Thermodilution and TEE CO determinations both had significant inverse correlation with the arterial-venous oxygen content difference in ten consecutive patients (r = 0.77, p < 0.01 and r = 0.71, p < 0.01, respectively). The correlation between variations of CO greater than 20 % obtained by thermodilution and TEE was significant (r = 0.89, p < 0.001). The operative characteristics implied the ability of TEE to predict significant variations of thermodilution CO (sensitivity 85 % and negative predictive values 86 %). Moreover, arterial-venous oxygen content difference changes of 5 % or more were better detected using TEE than thermodilution. Conclusions: These results suggest that although transesophageal CO measurements cannot replace thermodilution ones, the determination of CO variations obtained using TEE may be useful in the management of critically ill mechanically ventilated patients. This technique may make it possible to monitor hemodynamics during initial therapeutic interventions in those patients in whom right heart catheterization cannot be performed immediately.