Patient-ventilator trigger asynchrony in prolonged mechanical ventilation.

STUDY OBJECTIVE: To investigate patient-ventilator trigger asynchrony (TA), its prevalence, physiologic basis, and clinical implications in patients requiring prolonged mechanical ventilation (PMV). STUDY DESIGN: Descriptive and prospective cohort study. SETTING: Barlow Respiratory Hospital (BRH), a regional weaning center. PATIENTS: Two hundred consecutive ventilator-dependent patients, transferred to BRH over an 18-month period for attempted weaning from PMV. METHODS AND INTERVENTIONS: Patients were assessed clinically for TA within the first week of hospital admission, or once they were in hemodynamically stable condition, by observation of uncoupling of accessory respiratory muscle efforts and onset of machine breaths. Patients were excluded if they had weaned by the time of assessment or if they never achieved hemodynamic stability. Ventilator mode was patient triggered, flow control, volume cycled, with a tidal volume of 7 to 10 mL/kg. Esophageal pressure (Peso), airway-opening pressure, and airflow were measured in patients with TA who consented to esophageal catheter insertion. Attempts to decrease TA in each patient included application of positive end-expiratory pressure (PEEP) stepwise to 10 cm H2O, flow triggering, and reduction of ventilator support in pressure support (PS) mode. Patients were followed up until hospital discharge, when outcomes were scored as weaned (defined as >7 days of ventilator independence), failed to wean, or died. RESULTS: Of the 200 patients screened, 26 were excluded and 19 were found to have TA. Patients with TA were older, carried the diagnosis of COPD more frequently, and had more severe hypercapnia than their counterparts without TA. Only 3 of 19 patients (16%), all with intermittent TA, weaned from mechanical ventilation, after 70, 72, and 108 days, respectively. This is in contrast to a weaning success rate of 57%, with a median (range) time to wean of 33 (3 to 182) days in patients without TA. Observation of uncoupling of accessory respiratory muscle movement and onset of machine breaths was accurate in identifying patients with TA, which was confirmed in all seven patients consenting to Peso monitoring. TA appeared to result from high auto-PEEP and severe pump failure. Adjusting trigger sensitivity and application of flow triggering were unsuccessful in eliminating TA; external PEEP improved but rarely led to elimination of TA that was transient in duration. Reduction of ventilator support in PS mode, with resultant increased respiratory pump output and lower tidal volumes, uniformly succeeded in eliminating TA. However, this approach imposed a fatiguing load on the respiratory muscles and was poorly tolerated. CONCLUSION: TA can be easily identified clinically, and when it occurs in the patient in stable condition with PMV, is associated with poor outcome.

Post-ICU mechanical ventilation: treatment of 1,123 patients at a regional weaning center.

STUDY OBJECTIVES: To update our database, reporting changes in the results of weaning attempts and profile of patients transferred to us after prolonged mechanical ventilation (PMV) in the ICU. DESIGN: Retrospective record review, with prospective recording of physiologic measurements on admission from mid-1994. SETTING: Regional weaning center (RWC). PATIENTS: We studied 1,123 consecutive ventilator-dependent patients transferred for attempted weaning over an 8-year period. MEASUREMENTS AND RESULTS: Median (range) time of mechanical ventilation prior to transfer to the RWC declined from 37 (1 to 249) days in 1988 to 29 (1 to 120) days in 1996 (p<0.05). Acute physiology score of acute physiology and chronic health evaluation (APACHE) III was 32 (6 to 123) on RWC admission, equaling reported scores soon after ICU admission. Comparing other data on admission from 1988 to 1996, mean (+/-SD) serum albumin level declined from 2.92+/-0.58 to 2.43+/-0.50 g/dL, and alveolar-arterial oxygen pressure difference widened from 106+/-50 to 139+/-99 mm Hg. Prevalence of stage II or worse pressure ulceration on admission increased from 34% in 1988 to 46% in 1995. Despite these trends, there has been no significant change in patient outcome (55.9% weaned, 15.6% failed to wean, 28.8% died) or in median time to wean (29 [1 to 226] days). Overall survival at 1 year after discharge for the 8-year period is 37.9%, improving from 29% in 1988-1991 to 45% since 1992; survival in weaned patients discharged to home has improved from 45 to 59% during the respective time periods. CONCLUSIONS: Patients are being transferred from the ICU to our RWC for attempted weaning sooner in their course of PMV. Although more severely ill on arrival than in past years, mortality is unchanged, more than half of the patients continue to be successfully weaned, and survival after RWC discharge is improved.

Post-ICU weaning from mechanical ventilation: the role of long-term facilities.

A review of the largest observational studies on post-ICU weaning from prolonged mechanical ventilation yields evidence that more than half of such patients can be successfully liberated from mechanical ventilation. Success is likely to fall within a 3-month window, with late successes and partial ventilator independence still possible thereafter. There is a uniformity of practice in finishing difficult weaning with self-breathing trials of increasing duration.

Outcomes in post-ICU mechanical ventilation: a therapist-implemented weaning protocol.

BACKGROUND: Therapist-implemented protocols have been used to extubate or wean patients in the ICU setting. Barlow Respiratory Hospital (BRH) functions as a center for weaning patients from prolonged mechanical ventilation (PMV) in the post-ICU setting of a long-term acute-care (LTAC) facility. A therapist-implemented patient-specific (TIPS) weaning protocol was developed at BRH to standardize weaning from PMV. STUDY DESIGN: Prospective cohort study with historical control. METHODS: A weaning protocol incorporating the procedures and pace of LTAC weaning was developed using available scientific evidence and expert consensus. After training of staff, collection and analysis of pilot data, and revisions and refinement of the protocol, the TIPS protocol was implemented hospital-wide. It was monitored for outcome, variance, and respiratory care practitioner (RCP) and physician compliance. RESULTS: Forty-six RCPs worked with eight pulmonologists treating 271 consecutive patients admitted for weaning from PMV during an 18-month period. Nineteen patients were excluded from weaning attempts by any method after initial physician evaluation. The remaining 252 patients (9,135 total ventilator days) were compared with a group of 238 patients treated by the same physicians in the 2 years before instituting protocol weaning. Median time to wean declined significantly from 29 days in historical control subjects to 17 days for TIPS protocol patients (p < 0.001). Outcomes (scored at discharge) were comparable for the two groups (TIPS group vs control group): weaned, 54.7% vs 58.4%; ventilator-dependent, 17.9% vs 10.9%; died, 27.4% vs 30.7% (p = 0.10). Variances incurred by physicians and RCPs were 324 and 136, respectively, for the 9,135 ventilator days. CONCLUSIONS: Patients weaned from PMV using a new therapist-implemented protocol at BRH, an LTAC facility specializing in weaning, had significantly shorter time to weaning than historical control subjects, with comparable outcomes. The weaning outcome data collected after the implementation of the TIPS protocol are in fact attributable to its use, as we found a high degree of compliance with the protocol.

Weaning from mechanical ventilation.

For the ventilator-dependent patient, weaning should be accomplished by withdrawing support safely, efficaciously, and efficiently. Success depends largely on physiologic determinants of respiratory system function, avoidance of ventilator-associated complications, and attention to patient readiness. Recent clinical trials, predictors of weaning, current techniques of weaning, the concept of reloading the respiratory pump, and determinants of ventilator dependency are all discussed.

Approach to patients with long-term weaning failure.

Efforts to treat reversible disease processes that contribute to ventilator dependency in the intensive care unit (ICU) fail in up to 20% of patients, resulting in prolonged mechanical ventilation (PMV). Resolution of the insults that necessitated ICU admission and mechanical ventilation may be incomplete, and the economic pressure to transfer patients is ever increasing. The choice of post-ICU disposition depends on the patient's clinical condition, the resources of the transfer destination, and whether weaning attempts will continue. This article reviews data from a decade of weaning beyond the ICU, including outcomes of more than 2700 patients with PMV afforded continued attempts at liberation in long-term acute care facilities and other post-ICU weaning venues. Assessment and treatment, weaning strategies, and complications of patients with PMV are described.

An experimental study of using "tendon bridge" or "tendon tunnel" as a conduit for nerve regeneration.

In our experiments, a "tendon bridge" or a "tendon tunnel" was used as a conduit to repair the defect of a peripheral nerve in rabbits. A gap of about 1 cm was made on the deep peroneal nerve in each animal. In group 1, the tendon of anterior tibial muscle was isolated near the severed nerve, and a segment of half cross section of tendon was removed in ladder-shaped reversed fashion. The proximal and distal nerve stump were sutured respectively to the tendon by 11/0 atraumatic sutures under surgical microscope. In group 2, the nerve stumps were sutured to the tendon of anterior tibial muscle without cutting the tendon, but the tendon was dissected free and turned to form a tunnel wrapping the gap in between the nerve stumps. The results showed that a gap of 1 cm of the deep peroneal nerve might be repaired by both methods, but the results of using "tendon tunnel" in group 2 were much better than those of using "tendon bridge" in group 1.

Basolateral localization of Na(+)-HCO3- cotransporter activity in alveolar epithelial cells.

We investigated the polarized distribution of Na(+)- and HCO3(-)-dependent recovery from intracellular acidification in alveolar epithelial cell monolayers. Rat alveolar type II cells were grown in primary culture on detachable tissue culture-treated Nuclepore filters. Each filter was mounted in a cuvette containing two fluid compartments (apical and basolateral) separated by the monolayer. Cells were loaded with the pH-sensitive dye BCECF and intracellular pH (pHi) measured spectrofluorometrically. Monolayers were studied at ambient temperature on days 3-4 in culture, coincident with the development of high tissue resistance (RT > or = 1000 omega.cm2). After the cells were acidified by NH3 prepulse, pHi recovered to baseline when Na+ was present in the basolateral fluid, but did not recover when Na+ was present only in the apical fluid. This basolateral Na(+)-dependent pHi recovery in the presence of HCO3-/CO2 was reduced, but present, in experiments where dimethylamiloride (DMA, 100 microM) or the stilbene derivative DIDS (500 microM) was in basolateral fluid. However, recovery was completely inhibited when both DMA and DIDS were present basolaterally. pHi recovery was not inhibited under Cl(-)-free conditions, indicating that cytoplasmic realkalinization was not effected by Na(+)-dependent Cl-HCO3- exchange. These data indicate that alveolar epithelial cells express a basolateral Na(+)- and HCO3(-)-dependent, DIDS-sensitive, Cl(-)-independent pHi recovery process that probably represents Na(+)-HCO3(-)-cotransport (symport). Basolateral Na(+)-HCO3- cotransport modulates pHi in alveolar epithelial cells, may contribute to regulation of intracellular volume and osmolarity, and may participate in signal transduction by hormones and growth factors.

Molecular characterization of Gluconobacter oxydans recA gene and its inhibitory effect on the function of the host wild-type recA gene.

A DNA fragment containing the recA gene of Gluconobacter oxydans was isolated and further characterized for its nucleotide sequence and ability to functionally complement various recA mutations. When expressed in an Escherichia coli recA host, the G. oxydans recA protein could efficiently function in homologous recombination and DNA damage repair. The recA gene's nucleotide sequence analysis revealed a protein of 344 amino acids with a molecular mass of 38 kDa. We observed an E. coli-like LexA repressor-binding site in the G. oxydans recA gene promoter region, suggesting that a LexA-like mediated response system may exist in G. oxydans. The expression of G. oxydans recA in E. coli RR1, a recA+ strain, surprisingly caused a remarkable reduction of the host wild-type recA gene function, whereas the expression of both Serratia marcescens recA and Pseudomonas aeruginosa recA gene caused only a slight inhibitory effect on function of the host wild-type recA gene product. Compared with the E. coli RecA protein, the identity of the amino acid sequence of G. oxydans RecA protein is much lower than those RecA proteins of both S. marcescens and Pseudomonas aeruginosa. This result suggests that the expression of another wild-type RecA could interfere with host wild-type recA gene's function, and the extent of such an interference is possibly correlated to the identity of the amino acid sequence between the two classes of RecA protein.

Determination and Distribution of cry-Type Genes of Bacillus thuringiensis Isolates from Taiwan.

Using PCR with a set of specific oligonucleotide primers to detect cryI-type genes, we were able to screen the cry-type genes of 225 Bacillus thuringiensis soil isolates from Taiwan without much cost in time or labor. Some combinations of cry genes (the cry-type profile) in a single isolate were unique. We identified five distinct profiles of crystal genes from the B. thuringiensis soil isolates from Taiwan. The cry genes included cryIA(a), cryIA(b), cryIA(c), cryIC, cryID, and cryIV. Interestingly, 501 B. thuringiensis isolates (93.5% of the total number that we identified) were isolated from areas at high altitudes. The profiles of cry-type genes were distinct in all isolation areas. The distribution of cry-type genes of our isolates therefore depended on geography. Using PCR footprinting to detect cryIC-type genes, we identified two distinct cryIC footprints from some of our isolates, indicating that these isolates may contain novel cryIC-type genes. B. thuringiensis isolates containing cryIA(a)-, cryIA(b)-, and cryIA(c)-type genes exhibited much greater activity against Plutella xylostella than did other isolates, indicating that multiple cry-type genes may be used as markers for the prediction of insecticidal activities.

Cl(-)-HCO3- exchanger isoform AE2 is restricted to the basolateral surface of alveolar epithelial cell monolayers.

We investigated the polarized distribution and isoform specificity of anion exchange (Cl(-)-HCO3- exchange) in alveolar epithelial cell monolayers. Rat alveolar type II epithelial cell monolayers were grown in primary culture on detachable tissue culture-treated nuclepore filters. Each filter was mounted in a cuvette containing two fluid compartments (apical and basolateral) separated by the monolayer, the cells loaded with pH-sensitive dye, and intracellular pH (pHi) measured spectrofluorometrically. To assay for Cl(-)-HCO3- exchange, monolayers were incubated in medium containing 24 mM HCO3-/5% CO2 and 140 mM NaCl at pH 7.4 and acutely alkalinized by replacement of the fluid by HCO3(-)-free buffer containing Hepes (6 mM) at pH 7.4. Monolayers exhibited basolateral (but not apical) Cl(-)-dependent, Na(+)-independent recovery from an alkaline load that was abolished when Cl- was substituted by equimolar gluconate in the basolateral fluid, or if DIDS (500 microM) was present basolaterally. Substitution of gluconate for Cl- in the basolateral fluid, but not the apical fluid, resulted in a rise in steady-state pHi that was reversible on replacement of the basolateral fluid with Cl(-)-containing buffer, which occurred in HCO3(-)- but not Hepes-buffered medium. These data indicate that alveolar epithelial cells express basolateral membrane domain of these cells. Northern analysis of alveolar epithelial cell mRNA using anion exchanger (AE) isoform-specific cDNA probes indicates that alveolar epithelial cells express the AE2 isoform predominantly, if not exclusively, and do not express detectable AE1 (i.e., band-3 protein) or AE3.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequence analysis of the Gluconobacter oxydans RecA protein and construction of a recA-deficient mutant.

The deduced amino acid sequence of Gluconobacter oxydans RecA protein shows 75.2, 69.4, and 66.2% homology with those from Aquaspirillum magnetotacticum, Escherichia coli, and Pseudomonas aeruginosa, respectively. The amino acid residues essential for function of the recombinase, protease, and ATPase in E. coli recA protein are conserved in G. oxydans. Of 24 amino acid residues believed to be the ATP binding domain of E. coli RecA, 17 are found to be identical in G. oxydans RecA. Interestingly, nucleotide sequence alignment between the SOS box of G. orphans recA gene and those from different microorganisms revealed that all the DNA sequences examined have dyad symmetry that can form a stem-loop structure. A G. oxydans recA-deficient mutant (LCC96) was created by allelic exchange using the cloned recA gene that had been insertionally inactivated by a kanamycin-resistance cassette. Such replacement of the wild-type recA with a kanamycin resistance gene in the chromosome was further verified by Southern hybridization. Phenotypically, the recA-deficient mutant is significantly more sensitive to UV irradiation than the wild-type strain, suggesting that the recA gene of G. oxydans ATCC9324 plays a role in repairing DNA damage caused by UV irradiation. Moreover, the mutant strain is much more plasmid transformable than its parent strain, illustrating that G. oxydans LCC96 could be used as a host to take up the recombinant plasmid for gene manipulation.