Systemic absorption of endotracheally administered aminoglycosides in seriously ill patients with pneumonia.

A study was performed with 10 hospitalized patients to determine the percentage of an aminoglycoside dose (tobramycin or gentamicin) that is absorbed systemically after being instilled into the endotracheal tube at steady state. All patients were on respirators, had indwelling urinary catheters, and had creatinine clearances estimated to be greater than or equal to 40 ml/min. Tobramycin or gentamicin (40 mg) was instilled every 4 h directly into the endotracheal tube. Nine patients also received systemically a different aminoglycoside from that administered through the endotracheal tube. Urine was collected over a 4-h dosing interval at steady state (after at least 5 doses of the drug). The amount of aminoglycoside excreted over the 4-h interval was measured and expressed as percentage of the dose administered over that period. The range of percentage of dose absorbed was 1.5 to 34%, with a mean of 16.7 +/- 11.4% standard deviation and a median of 16.5%. The coefficient of variation was 68%. Levels of the endotracheally administered aminoglycoside in serum were measured, and all were less than 1.0 microgram/ml. While a large degree of variability in absorption was observed in this study, significant amounts of aminoglycosides could be absorbed in some patients. However, levels apparently did not accumulate in sera of patients with adequate renal function, and an empirical dosage reduction in intravenous aminoglycoside should not be necessary with the addition of endotracheally instilled aminoglycoside in patients with creatinine clearances greater than 40 ml/min.     

Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients.

Seventy-four acutely ill patients were treated with intravenous ciprofloxacin at dosages ranging between 200 mg every 12 h and 400 mg every 8 h. A population pharmacokinetic-pharmacodynamic analysis relating drug exposure (and other factors) to infectious outcome was performed. Plasma samples were obtained and assayed for ciprofloxacin by high-performance liquid chromatography. Samples from patients were frequently cultured so that the day of bacterial eradication could be determined. The pharmacokinetic data were fitted by iterative two-stage analysis, assuming a linear two-compartment model. Logistic regression was used to model ciprofloxacin exposure (and other potential covariates) versus the probabilities of achieving clinical and microbiologic cures. The same variables were also modelled versus the time to bacterial eradication by proportional hazards regression. The independent variables considered were dose, site of infection, infecting organism and the MIC for it, percent time above the MIC, peak, peak/MIC ratio, trough, trough/MIC ratio, 24-h area under the concentration-time curve (AUC), AUC/MIC ratio (AUIC), presence of other active antibacterial agents, and patient characteristics. The most important predictor for all three measures of ciprofloxacin pharmacodynamics was the AUIC. A 24-h AUIC of 125 SIT-1.h (inverse serum inhibitory titer integrated over time) was found to be a significant breakpoint for probabilities of both clinical and microbiologic cures. At an AUIC below 125 (19 patients), the percent probabilities of clinical and microbiologic cures were 42 and 26%, respectively. At an AUIC above 125 (45 patients), the probabilities were 80% (P < 0.005) and 82% (P < 0.001), respectively. There were two significant breakpoints in the time-to-bacterial-eradication data. At an AUIC below 125 (21 patients), the median time to eradication exceeded 32 days; at an AUIC of 125 to 250 (15 patients), time to eradication was 6.6 days: and at AUIC above 250 (28 patients), the median time to eradication was 1.9 days (groups differed; P < 0.005). These findings, when combined with pharmacokinetic data reported in the companion article, provide the rationale and tools needed for targeting the dosage of intravenous ciprofloxacin to individual patients' pharmacokinetics and their bacterial pathogens' susceptibilities. An a priori dosing algorithm (based on MIC, patient creatine clearance and weight, and the clinician-specified AUIC target) was developed. This approach was shown, retrospectively, to be more precise than current guidelines, and it can be used to achieve more rapid bacteriologic and clinical responses to ciprofloxacin, as a consequence of targeting the AUIC.     

Effects of midazolam on electroencephalograms of seriously ill patients.

Midazolam hydrochloride, a water-soluble benzodiazepine for intravenous injection, is frequently used to provide sedation to mechanically ventilated patients in the critical-care unit. Although the effects of midazolam on the electroencephalograms (EEGs) of healthy volunteers have been reported previously, to our knowledge such effects in ill patients have not been documented. Herein we describe the effects of intravenously administered midazolam on the EEGs of eight seriously ill patients (age range, 49 to 80 years; mean, 69 years). The EEGs showed drug-induced relatively fast (alpha or beta) frequency activity superimposed on delta slowing in six patients and mild to moderate voltage attenuation in three patients. An alpha frequency coma pattern, a transient burst-suppression pattern, and a spindle coma pattern were also seen. Thus, the effects of intravenously administered midazolam on the EEGs of seriously ill patients are similar to those noted after the administration of other benzodiazepines. These potential effects should be considered when their EEG tracings are interpreted.     

Prevention and care of ventilator-associated pneumonia in critically ill patients

Ventilator-associated pneumonia (VAP) is a hospital-acquired pneumonia that occurs in patients usually 48 hours or more after mechanical ventilator intubation. VAP is the most common nosocomial infection in critically ill patients. Mechanical ventilators are critical oxygenation and ventilation systems for patients. However, there is a close relationship among self-use efficacy, system settings, and VAP infection rate. VAP not only results in higher mortality, longer hospital stays, and higher medical costs, but also negatively affects patient outcomes and medical care quality. The purpose of this article was to provide reference information on VAP risk factors and prevention measures.     

Antibiotic prophylaxis of early onset pneumonia in critically ill comatose patients. A randomized study

Objective To evaluate if a 3-day ampicillin-sulbactam prophylaxis can reduce the occurrence of early-onset pneumonia (EOP) in comatose mechanically-ventilated patients.Design This was a single-centre, prospective, randomised, open study.Setting A 10-bed general-neurological ICU in a 2,000-bed university hospital.Patients and participants Comatose mechanically-ventilated patients with traumatic, surgical or medical brain injury.Interventions Patients were randomized to either ampicillin-sulbactam prophylaxis (3 g every 6 h for 3 days) plus standard treatment or standard treatment alone.Measurements and results Main outcome was the occurrence of EOP. Secondary outcome measures were occurrence of late-onset pneumonia, percentage of non-pulmonary infections and of emerging multiresistant bacteria, duration of mechanical ventilation and of ICU stay and ICU mortality. Interim analysis at 1 year demonstrated a statistically significant reduction of EOP in the ampicillin-sulbactam group, and the study was interrupted. Overall, 39.5% of the patients developed EOP, 57.9% in the standard treatment group and 21.0% in the ampicillin-sulbactam group (chi-square 5.3971; P =0.022). Relative risk reduction of EOP in patients receiving ampicillin-sulbactam prophylaxis was 64%; the number of patients to be treated to avoid one episode of EOP was three. No differences in other outcome parameters were found; however, the small sample size precluded a definite analysis.Conclusions Antibiotic prophylaxis with ampicillin-sulbactam significantly reduced the occurrence of EOP in critically ill comatose mechanically ventilated patients. This result should encourage a large multicenter trial to demonstrate whether ampicillin-sulbactam prophylaxis reduces patient mortality, and whether antibiotic resistance is increased in patients receiving prophylaxis.     

Pentamidine aerosol in prophylaxis and treatment of murine Pneumocystis carinii pneumonia.

The efficacy and tolerance of pentamidine aerosol were evaluated in the prophylaxis and therapy of murine Pneumocystis carinii pneumonia. P. carinii pneumonia was induced in rats by corticosteroid immunosuppression. Pentamidine was administered three times weekly via a Bird micronebulizer. The actual amount of pentamidine inhaled was estimated by monitoring the ventilation of the rats during the aerosol administration. Pentamidine levels in blood, lung, liver and kidney samples were determined by high-pressure liquid chromatography after completion of the treatment. Efficacy was evaluated by examination of lung imprints. In the prophylactic treatment, 4.8- and 8.6-mg/kg doses of aerosolized pentamidine administered three times weekly for 7 weeks were effective in preventing P. carinii pneumonia in 80 and 100% of the rats, respectively. In the therapeutic studies, a 14.6-mg/kg dose of aerosolized pentamidine administered three times weekly for 3 weeks was effective both in curing the pneumonia and in clearing P. carinii cysts in 70% of the rats. In the remaining animals, although the pneumonia was cured, the cysts persisted. A dose-dependent effect of the drug was demonstrated in both prophylactic and therapeutic treatments. High lung/kidney and lung/liver ratios of pentamidine levels were demonstrated and were associated with good clinical, biological, and histologic tolerance.     

Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial

Purpose

To evaluate the potential preventive effect of probiotics on ventilator-associated pneumonia (VAP).

Methods

This was an open-label, randomized, controlled multicenter trial involving 235 critically ill adult patients who were expected to receive mechanical ventilation for ≥48 h. The patients were randomized to receive (1) a probiotics capsule containing live Bacillus subtilis and Enterococcus faecalis (Medilac-S) 0.5 g three times daily through a nasogastric feeding tube plus standard preventive strategies or (2) standard preventive strategies alone, for a maximum of 14 days. The development of VAP was evaluated daily, and throat swabs and gastric aspirate were cultured at baseline and once or twice weekly thereafter.

Results

The incidence of microbiologically confirmed VAP in the probiotics group was significantly lower than that in the control patients (36.4 vs. 50.4 %, respectively; P = 0.031). The mean time to develop VAP was significantly longer in the probiotics group than in the control group (10.4 vs. 7.5 days, respectively; P = 0.022). The proportion of patients with acquisition of gastric colonization of potentially pathogenic microorganisms (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (P = 0.004). However, the proportion of patients with eradication PPMO colonization on both sites of the oropharynx and stomach were not significantly different between the two groups. The administration of probiotics did not result in any improvement in the incidence of clinically suspected VAP, antimicrobial consumption, duration of mechanical ventilation, mortality and length of hospital stay.

Conclusion

Therapy with the probiotic bacteria B. Subtilis and E. faecalis are an effective and safe means for preventing VAP and the acquisition of PPMO colonization in the stomach.

     

Peptide-binding macromolecules in the blood of seriously ill or mentally retarded patients.

This report describes macromolecules that bind (des-aspartic acid1)-angiotensin II, the des aspartic acid1 derivative of angiotensin I, and several biologically active and inactive analogues of these polypeptides. The macromolecules were found in the plasma of approximately 2 per cent of ambulatory adults and hospitalized children and 32 per cent of the patients at two institutions for the mentally retarded. The binding properties of these macromolecules were studied by incubating with peptides labeled with 125iodine, and separating bound from free labeled peptide using small gel filtration columns. The peptide-binding macromolecules from several patients were compared. They showed very similar specificity for a group of arginyl peptides of the des-aspartyl1-angiotensin sequence. The plasma binders differed from one another in their optimum pH and their mobility in electrophoretic fields. Those with more acid pH optima displayed more rapid electrophoretic mobility. The binders fell into two classes based on apparent molecular weight, approximately 140,000 and 250,000. Those with the higher apparent molecular weight contained a large proportion of binder that could be precipitated with antiserum to human IgA. Kinetic measurements showed that the plasma binders were somewhat heterogeneous with respect to affinity for (des-asp1)-angiotensin, with apparent association constants ranging from 10(7) to 10(8) M-1. Binding activity was labile to heat, and to treatment with pepsin or trypsin. It was inhibited by calcium, protamine, streptomycin, and some other cationic compounds. The plasma peptide binder differed in specificity and molecular weight from soluble angiotensin-binding molecules extracted from tissues, and from properties expected of a receptor for angiotensin. These macromolecules may be useful reagents for measuring (des-asp1)-angiotensins. Their presence in plasma samples may interfere with angiotensin assays in some circumstances.     

Disease-specific patterns of hospice and related healthcare use in an incidence cohort of seriously ill elderly patients

There appears to be significant heterogeneity across diseases in their patterns of health care use at the end of life. We use a new, nationally representative sample of patients diagnosed in 1993 with 13 serious diseases to demonstrate this variation in rates of inpatient, outpatient, and hospice utilization. The diseases are: cancer of the lung, colon, pancreas, urinary tract, liver or biliary tract, head or neck, or central nervous system, as well as leukemia or lymphoma, stroke, congestive heart failure, hip fracture, or myocardial infarction. We present disease-specific rates of: length of stay, interhospital transfer, outpatient visits in the year before and 3 years after diagnosis, death within 4 years, and gender-specific hospice use rates among decedents. Among decedents with noncancer diagnoses, rates of hospice use vary from 5.9% to 8.7%. Among decedents with cancer diagnoses, rates vary from 15.2% to 35.2%. For the cohort overall, 14.2% of male decedents and 12.4% of female decedents used hospice. Patterns of end-of-life care vary substantially according to diagnosis.     

Safety and efficacy of high-dose treatment with imipenem-cilastatin in seriously ill patients.

Imipenem-cilastatin was given in doses of 1 g intravenously every 6 h to 31 patients. Twenty-five patients, with 27 infections, were clinically evaluable and received 20 to 210 g of imipenem for a duration of 5 to 56 days (average 16.3 days). Infections included seven cases of osteomyelitis, seven of bacteremia, five of cellulitis, two of pneumonia, three of pelvic cellulitis, two of intraabdominal abscess, and one each of empyema, mediastinitis, and endometritis. Fifty-five percent of the infections were caused by gram-negative bacilli, 33% were due to gram-positive organisms, and 10% were caused by anaerobes. Twenty-two patients (81%) were cured, three improved, one relapsed, and one became superinfected with a resistant organism. In 5 of 11 cases with Pseudomonas aeruginosa, the imipenem MIC for organisms isolated by the end of treatment was higher than it was initially, raising concern that imipenem should not be used alone to treat Pseudomonas aeruginosa infections. Twenty-one patients had no adverse reaction; of the remaining 10 patients, 4 had nausea, 1 had urticaria, and 6 had mild abnormalities in hepatic function; three episodes of diarrhea included two with Clostridium difficile toxin in stool and one with pseudomembranous colitis, as determined by sigmoidoscopy. Levels of creatinine, hemoglobin, leukocytes, platelets, prothrombin, and urine components were unchanged. Imipenem-cilastatin is a clinically effective antibiotic with freedom from nephrotoxicity and hematological abnormalities in the large doses used in this study.     

Probiotics' effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis

ABSTRACT: INTRODUCTION: To evaluate the efficacy of probiotics in preventing nosocomial pneumonia in critically ill patients. METHODS: We searched PubMed, EMBASE, and the Web of Science for relevant studies. Two reviewers extracted data and reviewed the quality of the studies independently. The primary outcome was the incidence of nosocomial pneumonia. Study-level data were pooled using a random-effects model when I2 was > 50% or a fixed-effects model when I2 was < 50%. RESULTS: Twelve randomized controlled studies with a total of 1,546 patients were considered. Pooled analysis showed a statistically significant reduction in nosocomial pneumonia rates due to probiotics (odd ratio [OR]= 0.75, 95% CI 0.57 to 0.97, P = 0.03, I2 = 46%). However, no statistically significant difference was found between groups regarding in-hospital mortality (OR = 0.93, 95% CI 0.50 to 1.74, P = 0.82, I2 = 51%), intensive care unit mortality (OR = 0.84, 95% CI 0.55 to 1.29, P = 0.43, I2 = 0%), duration of stay in the hospital (mean difference [MD] in days = -0.13, 95% CI -0.93 to 0.67, P = 0.75, I2 = 46%), or duration of stay in the intensive care units (MD = -0.72, 95% CI -1.73 to 0.29, P = 0.16, I2 = 68%). CONCLUSIONS: The use of probiotics was associated with a statistically significant reduction in the incidence of nosocomial pneumonia in critically ill patients. However, large, well-designed, randomized, multi-center trials are needed to confirm any effects of probiotics clinical endpoints such as mortality and length of ICU and hospital stay.     

Probiotics' effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis

Introduction

Transpulmonary thermodilution is used to measure cardiac output (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A system has been introduced (VolumeView/EV1000? system, Edwards Lifesciences, Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of the thermodilution curve. Our aim was to evaluate the agreement of this method with the established PiCCO? method (Pulsion Medical Systems SE, Munich, Germany, clinicaltrials.gov identifier: NCT01405040)

Methods

Seventy-two critically ill patients with clinical indication for advanced hemodynamic monitoring were included in this prospective, multicenter, observational study. During a 72-hour observation period, 443 sets of thermodilution measurements were performed with the new system. These measurements were electronically recorded, converted into an analog resistance signal and then re-analyzed by a PiCCO₂? device (Pulsion Medical Systems SE).

Results

For CO, GEDV, and EVLW, the systems showed a high correlation (r² = 0.981, 0.926 and 0.971, respectively), minimal bias (0.2 L/minute, 29.4 ml and 36.8 ml), and a low percentage error (9.7%, 11.5% and 12.2%). Changes in CO, GEDV and EVLW were tracked with a high concordance between the two systems, with a traditional concordance for CO, GEDV, and EVLW of 98.5%, 95.1%, and 97.7% and a polar plot concordance of 100%, 99.8% and 99.8% for CO, GEDV, and EVLW, respectively. Radial limits of agreement for CO, GEDV and EVLW were 0.31 ml/minute, 81 ml and 40 ml, respectively. The precision of GEDV measurements was significantly better using the VolumeView? algorithm compared to the PiCCO? algorithm (0.033 (0.03) versus 0.040 (0.03; median (interquartile range), P = 0.000049).

Conclusions

For CO, GEDV, and EVLW, the agreement of both the individual measurements as well as measurements of change showed the interchangeability of the two methods. For the VolumeView method, the higher precision may indicate a more robust GEDV algorithm.

Trial registration

clinicaltrials.gov NCT01405040.     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

Hypoalbuminemia as an indicator of diarrheal incidence in critically ill patients

Recently, we noted that substantial numbers of critically ill patients admitted to a medical ICU developed diarrhea. We checked them for infectious, metabolic, and untoward medication effects, which were negative. We next considered a possible causal relation between reduced serum albumin and diarrhea. To document the frequency of diarrhea in this population, explore the relation between hypoalbuminemia and diarrhea, and make a preliminary assessment of a peptide-based, chemically defined diet in these catabolic patients, a study of consecutive medical ICU patients was begun. For each patient, we recorded the principal diagnosis, type of diet received, the frequency and volume of stool, and the serum albumin concentration at admission. When diarrhea developed, attention was paid to the serum albumin levels as well as the effects of various diets. Overall, 12 (34%) of 35 study patients developed diarrhea. No patient had a previous history of diarrhea, malabsorption, weight loss, or GI symptoms that may precede the onset of diarrhea. The stools from each patient with diarrhea were examined for enteric pathogens, ova and parasites, Clostridium difficile culture and cytotoxin assay, and qualitative stool fat, which were all negative. Every patient with a serum albumin level less than 2.6 g/dl developed diarrhea. No patient with a serum albumin level of 2.6 g/dl or greater developed diarrhea, regardless of the type of nutritional support received. Four of the 12 patients with hypoalbuminemia and diarrhea were placed on a peptide-based, chemically defined diet, after which their diarrhea resolved and their serum albumin concentrations increased.     

危重病患者早期肠内营养预防应激性溃疡的观察及护理

目的 :验证早期肠内营养对重症患者应激性溃疡的预防作用 ,并对这类患者的护理注意事项进行探讨。方法 :对 77例进ICU的危重患者随机分成早期肠内营养组 (42例 )和延迟肠内营养组 (35例 ) ,分别对每例患者的胃液及粪便进行不同时间段的隐血情况监测 ,并对监测结果进行统计学处理。结果 :早期肠内营养组与延迟肠内营养组上消化道出血发生分别为 4 / 4 2和 15 / 35例 (P <0 .0 0 1)。结论 :早期肠内营养对危重患者应激性溃疡的发生有一定的预防作用。     

危重病患者早期肠内营养应激性溃疡的预防及护理

目的 :验证早期肠内营养对重症患者应激性溃疡的预防作用 ,并总结临床护理经验。方法 :随机将入院ICU的危重患者 77例分成早期肠内营养组 (4 2例 )和延迟肠内营养组 (35例 ) ,分别监测每例患者不同时间段的胃液及粪便的隐血情况 ,并对监测结果进行统计学处理。结果 :早期肠内营养组与延迟肠内营养组上消化道出血发生分别为 4 / 4 2和 15 / 35 (P <0 0 0 1)。结论 :早期肠内营养对危重患者应激性溃疡的发生有一定的预防作用。     

Effect of a rotating bed on the incidence of pulmonary complications in critically ill patients

The risk of nosocomial pneumonia and atelectasis is high among critically ill immobilized patients. We hypothesized that continuous turning on the kinetic treatment table would reduce their incidence. Sixty-five critically ill patients, immobilized because of head injury or traction, were prospectively randomized for treatment in a conventional bed (n = 38) or the kinetic treatment table (n = 27). Patients were well matched for baseline demographic and pulmonary risk factors. Patients in the conventional bed group had a higher incidence of cigarette smoking. The combined incidence of significant atelectasis or pneumonia was higher (66%) in the conventional vs. kinetic treatment table (33%) groups (p less than .01). Atelectasis, pneumonia, adult respiratory distress syndrome, requirements for ventilator treatment, for PEEP, and for an FIO2 greater than 0.50 were not significantly different, but tended to be higher in the control group. Survival and the incidence of decubitus ulcers were similar.     

护理干预内容列入重症病人评估积分的研究与探讨

目的了解一级护理以上病人所需治疗护理干预的内容和所需时间,以帮助护理管理者科学评价病人危重程度和科室工作量,使之成为对重症病人进行科学指导、监控、合理调配护理人员的可靠依据。方法根据168项重症病人常用的护理内容评价表,对一级护理以上206名病人治疗干预内容进行了调查。结果选择出5大类,31项重症病人最常用的治疗护理干预措施内容,纳入重症病人积分,以促使各级护理人员认真落实重症病人各项护理措施,同时护理管理人员也将其作为重症病人的质量监控点,为重症护理质量控制、合理调配利用护理人力资源提供可靠依据。