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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Recently, subclassification of pancreatoduodenectomy in 4 differing types has been reported, because additional major vascular and multivisceral resections have been shown to be associated with an increased risk of postoperative morbidity and mortality., Objective: To classify distal pancreatectomy (DP) based on the extent of resection and technical difficulty and to evaluate postoperative outcomes with regards to this classification system., Methods: All consecutive patients who had undergone DP between 2001 and 2020 in a high-volume pancreatic surgery center were included in this study. DPs were subclassified into 4 distinct categories reflecting the extent of resection and technical difficulty, including standard DP (type 1), DP with venous (type 2), multivisceral (type 3), or arterial resection (type 4). Patient characteristics, perioperative data, and postoperative outcomes were analyzed and compared among the 4 groups., Results: A total of 2135 patients underwent DP. Standard DP was the most frequently performed procedure (64.8%). The overall 90-day mortality rate was 1.6%. Morbidity rates were higher in patients with additional vascular or multivisceral resections, and 90-day mortality gradually increased with the extent of resection from standard DP to DP with arterial resection (type 1: 0.7%; type 2: 1.3%; type 3: 3%; type 4: 8.7%; P <0.0001). Multivariable analysis confirmed the type of DP as an independent risk factor for 90-day mortality., Conclusions: Postoperative outcomes after DP depend on the extent of resection and correlate with the type of DP. The implementation of the 4-type classification system allows standardized reporting of surgical outcomes after DP improving comparability of future studies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Up to 50% of patients with colorectal cancer (CRC) have either synchronous or metachronous hepatic metastases in the course of their disease. Patients with metastatic CRC (mCRC) whose tumors express wild-type KRAS benefit from treatment with monoclonal antibodies (such as cetuximab or panitumumab) that target the epidermal growth factor receptor (EGFR). However, the therapeutic response to these antibodies is variable, and further predictive models are required. The present study examined whether expression of different EGFRs or their ligands in tumors was associated with the response to cetuximab treatment. Tumor tissues, collected during liver resection in 28 patients with mCRC, were analyzed. The protein expression levels of EGFR/ErbB1, ErbB2, ErbB3 and the EGFR ligands heregulin and amphiregulin were determined using Luminex 200 ® and enzyme-linked immunosorbent assays. Computed tomography or magnetic resonance imaging was performed 4 weeks before and 6-8 weeks after treatment with cetuximab. Response to treatment was assessed using the response evaluation criteria for solid tumors (RECIST). The association between the protein expression levels of different EGFRs and their ligands with RECIST criteria was then analyzed to determine whether these protein levels could predict the treatment response to cetuximab. A total of 12 patients exhibited a partial response, 9 exhibited stable disease and 7 exhibited progressive disease after cetuximab therapy according to RECIST. The expression levels of EGFRs (EGFR/ErbB1, ErbB2 and ErbB3) and their ligands (heregulin and amphiregulin) were not significantly associated with the response to cetuximab therapy. Therefore, the present study indicated that EGFR or EGFR ligand expression did not predict treatment response in patients with CRC with liver metastases following cetuximab therapy., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021, Spandidos Publications.)

Background: Solid pseudopapillary neoplasms (SPN) are rare and represent approximately 4% of all cystic pancreatic tumors. The prognosis is excellent, although 10-15% of SPN patients show metastasis at the time of surgery or tumor recurrence during follow-up after pancreatectomy. Aim of the study was to analyze surgical management, risk factors for malignancy as well as long-term outcome and prognosis of this distinct tumor entity., Method: All patients with pancreatic resection for SPN between 10/2001 and 07/2018 in the authors' institution were identified from a prospective database. Clinicopathologic details, perioperative data and long-term follow-up results were retrospectively analyzed., Results: Fifty-two patients were identified, 44 (85%) of them were female and the median age was 29 years (IQR 9-71). Seven (13%) patients showed a malignant behaviour of SPN with N1 (n = 2) or M1 (n = 1) disease at resection; 5 patients developed tumor recurrence, after a median of 21 months. During follow-up time (median 54 months) all patients were alive, the 5- and 10-year rates for disease-free survival were 89.0% and 81.6%, respectively. Significant risk factors for recurrence were age <18 years (p = 0.0087) and parenchyma-preserving surgical approaches (p = 0.0006). The postoperative long-term outcome showed ECOG = 0-1 in all patients, with resection related exocrine insufficiency in 20 (41%) and diabetes mellitus in 2 (4%) patients., Conclusions: Age < 18 years is a significant risk factor for malignancy in SPN, and parenchyma preserving resections harbor a significant risk for tumor recurrence. As recurrence may occur late, a systematic life-long follow-up should be performed., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC)., Background: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC., Methods: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival., Results: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200 mL (60-400) vs 300 mL (150-500), P = 0.001] and hospital stay [8 (6-12) vs 9 (7-14) days, P < 0.001] were lower after MIDP. Clavien-Dindo grade ≥3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P > 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P < 0.001) and lymph node retrieval [14 (8-22) vs 22 (14-31), P < 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22-34] versus 31 (95% CI, 26-36) months (P = 0.929)., Conclusions: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

Background: Perioperative and short-term postoperative parameters are similar comparing spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). But there are no sound data evaluating the long term risk of postoperative thromboses and infectious complications after splenectomy. The present study evaluated whether the coagulation status differs in patients after SPDP and DPS, and whether that matters clinically., Methods: A total of 41 patients after DP (SPDP = 20; DPS = 21) were followed up, focusing on alterations of patient coagulation and immune status. To assess kinetics of the coagulation process, qualitative tests (multiple platelet function analyzer, rotational thrombelastography) were used in addition to global coagulation tests., Results: Coagulation tests revealed a significant enhanced tendency for blood-platelet aggregation and coagulation activation in patients after DPS compared to patients after SPDP. No septic or thromboembolic events were observed in any patient., Conclusion: Hypercoagulability in splenectomized patients persists over years. Thus, a correlation of this finding with thromboembolic events and mortality years after splenectomy should to be performed in a large cohort., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to analyze the impact of teres ligament covering on pancreatic fistula rate after distal pancreatectomy (DP)., Background: Postoperative pancreatic fistula (POPF) represents the most significant complication after DP. Retrospective studies suggested a benefit of covering the resection margin by a teres ligament patch., Methods: This prospective randomized controlled study (DISCOVER trial) included 152 patients undergoing DP, between October 2010 and July 2014. Patients were randomized to undergo closure of the pancreatic cut margin without (control, n = 76) or with teres ligament coverage (teres, n = 76). The primary endpoint was the rate of POPF, and the secondary endpoints included postoperative morbidity and mortality, length of hospital stay, and readmission rate., Results: Both groups were comparable regarding epidemiology (age, sex, body mass index), operative parameters (operation time [OP] time, blood loss, method of pancreas transection, additional operative procedures), and histopathological findings. Overall inhospital mortality was 0.6% (1/152 patients). In the group of patients with teres ligament patch, the rate of reoperations (1.3% vs 13.0%; P = 0.009), and also the rate of readmission (13.1 vs 31.5%; P = 0.011) were significantly lower. Clinically relevant POPF rate (grade B/C) was 32.9% (control) versus 22.4% (teres, P = 0.20). Multivariable analysis showed teres ligament coverage to be a protective factor for clinically relevant POPF (P = 0.0146)., Conclusions: Coverage of the pancreatic remnant after DP is associated with less reinterventions, reoperations, and need for readmission. Although the overall fistula rate is not reduced by the coverage procedure, it should be considered as a valid measure for complication prevention due to its clinical benefit.

Background: Fluid collections (FC) at the resection margin of the pancreatic stump after distal pancreatectomy (DP) are common radiological findings in follow-up scans. No recommendations exist regarding the management of such findings. The aim was to characterise incidence, risk factors, clinical impact and therapy of FC., Method: Data of 209 patients who underwent DP between 07/2009 and 06/2011 were prospectively collected and analysed, regarding follow-up CT or MRI scan findings of FC at the resection margin. FC was defined as a cyst-like lesion >1 cm in diameter., Results: A follow-up with at least two cross-sectional images was available in 159/209 patients. In the first postoperative control, 68 patients showed an FC (43%). FC size was classified as <5 cm (n = 38 pat.), 5-10 cm (n = 24 pat.) and >10 cm (n = 6 pat.). 20 patients (30%) showed clinical symptoms. Six patients (9%) required specific treatment, all other FC showed spontaneous regression. No correlation with stump closure techniques or preceding postoperative pancreatic fistula was found (4/68 patients, 6%). Multivariate analysis revealed standard resections as the only significant factor for FC., Conclusions: FCs at the resection margin after DP are frequent and harmless findings. Therapeutic interventions are required in only 9% of all FC patients., (Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. PDAC cells activate tumor-specific immune responses but simultaneously trigger a strong immunosuppression. We showed that PDAC cells produce high amount of chronic inflammatory mediators and PDAC tumors build an immunosuppressive cytokine milieu, which correlates with tumor progression. We observed a low frequency of dendritic cells (DC) and a pronounced accumulation of macrophages and myeloid-derived suppressor cells (MDSC) in murine PDAC tumors. A strong accumulation of MDSC has also been demonstrated in the peripheral blood of resected PDAC patients. While DC and macrophages seem not to play a significant role in this PDAC model in the context of immunosuppression, MDSC are highly suppressive, and their accumulation is associated with an increase in intratumoral VEGF concentration during the PDAC progression. Application of the phosphodiesterase-5 inhibitor sildenafil led to a prolonged survival of PDAC-bearing female mice, which was due to the decrease in MDSC frequencies and in the systemic VEGF level. This led to a restoration of anticancer immune responses, manifested in the recovery of T lymphocyte functions and in an increase in the frequency of conventional CD4 + T cells in tumors and IFNγ level in serum of PDAC-bearing mice. Thus, MDSC are strongly involved in the PDAC-associated immunosuppression and that their depletion could create new approaches for therapy of PDAC.

Estrogen regulates several biological processes in health and disease. Specifically, estrogen exerts antihypertrophic effects in the diseased heart. However, its role in the healthy heart remains elusive. Our initial aim was to identify the effects of 17β-estradiol (E2) on cardiac morphology and global gene expression in the healthy mouse heart. Two-month-old C57BL/6J mice were ovariectomized and treated with E2 or vehicle for 3 months. We report that E2 induced physiological hypertrophic growth in the healthy C57BL/6J mouse heart characterized by an increase in nuclear β-catenin. Hypothesizing that β-catenin mediates these effects of E2, we employed a model of cardiac β-catenin deletion. Our surprising finding is that E2 had the opposite effects in wild-type littermates, which were actually on the C57BL/6N background. Notably, E2 exerted no significant effect in hearts of mice with depleted β-catenin. We further demonstrate an E2-dependent increase in glycogen synthase kinase 3β (GSK3β) phosphorylation and endosomal markers in C57BL/6J but not C57BL/6N mice. Together, these findings indicate an E2-driven inhibition of GSK3β and consequent activation of β-catenin in C57BL/6J mice, whereas the opposite occurs in C57BL/6N mice. In conclusion, E2 exerts divergent effects on postnatal cardiac growth in mice with distinct genetic backgrounds modulating members of the GSK3β/β-catenin cascade.

Background: Distal pancreatectomy for benign and malignant tumours is the second most common surgical procedure on the pancreas. Postoperative pancreatic fistulas (POPF) represent the most significant clinical complication, causing prolongation of hospital stay and the need for additional diagnostic and therapeutic procedures. Although various techniques for preventing POPF have been evaluated, to date, there is no available technique that ensures closure of the pancreatic remnant., Methods/design: DISCOVER will aim to investigate differences in the postoperative course after a distal pancreatectomy comparing the standard surgical technique with an alternative technique that provides additional coverage of the pancreatic remnant by the falciform ligament. The primary endpoint of this trial will be the rate of POPF. As secondary endpoints, incidence of postoperative morbidity and mortality, length of hospital stay, and quality of life will be assessed.DISCOVER is a single-centre, randomised, controlled surgical trial. For statistical analysis, a binary logistic regression model will be used. With a level of significance of 5% and a power of 80%, a sample size of 75 patients per group has been identified as necessary., Discussion: The findings of this trial will help to evaluate the usefulness of the coverage procedure at reducing the rate of POPF. The results could influence the standard procedure for remnant closure after distal pancreatectomy., Trial-Registration: Clinical trials register (DRKS-ID: DRKS00000546).

Background: Pancreatic fistulas after distal pancreatectomy occur in up to 60% of patients with distal pancreatectomy. Several techniques for closure of the pancreatic stump have been advocated, but the best management of stump closure remains controversial. Our aim was to evaluate the clinical benefits of coverage of the pancreatic resection margin by autologous tissue., Methods: One hundred seventeen consecutive patients underwent distal pancreatectomy at the university hospital in Heidelberg between May 2009 and September 2010. A coverage procedure was performed in 73 of these patients. All patients were recorded prospectively, and the clinical course was evaluated focusing on the occurrence of pancreatic fistula as defined by the International Study Group on Pancreatic Fistula. A treatment cost analysis was performed., Results: The rate of clinically relevant pancreatic fistulas (types B and C) was decreased in patients with coverage compared to the standard controls (type B, 7% vs 9%; type C, 7% vs 25%; P < .002). Patients with a coverage procedure had a shorter duration of stay in the hospital (P < .02), and treatment costs were lower (P < .001) compared to patients without coverage., Conclusion: Coverage of the pancreatic remnant after distal pancreatectomy decreases the rate of clinically relevant pancreatic fistulas, duration of stay, and treatment costs. A randomized trial is needed to verify these results., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Circulating tissue factor (TF) is associated with inflammation and may contribute to thrombotic events. Aim of this study was to analyze circulating TF activity and proinflammatory cytokines in patients with deep venous thrombosis., Patients and Methods: Forty-eight patients with deep vein thrombosis and 45 control subjects were included. Venous blood samples were obtained at diagnosis for analysis of TF activity, TF antigen, prothrombin fragment F1 + 2, microparticles (expressing phosphatidylserine and supporting FXa generation), Interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12 and tumor-necrosis-factor-alpha (TNF)., Results: TF antigen, activity and microparticles were similar in both groups: In contrast, a significant increase in plasma IL-6, IL-8 and F1 + 2 levels was found in thrombosis. This increase in IL-6 and IL-8 as well as F1 + 2 was not correlated with the extent of thrombosis, predisposing factors or onset of symptoms., Conclusions: Circulating TF and microparticles are not elevated in deep venous thrombosis. The increase in IL-6, IL-8 and F1 + 2 during thrombosis was not proportional to the extent or predisposing risk factors.

Objective: To evaluate the safety and outcome of multivisceral pancreatic resections for primary pancreatic malignancies., Background: Curative resection is the only potential cure for patients with pancreatic cancer, but some patients present with advanced tumors that are not resectable by a standard pancreatic resection. Data on risk and survival analysis of extended pancreatic resections is limited., Methods: One hundred one patients who had a multivisceral pancreatic resection between 10/2001 and 12/2007 were identified from a prospective database, and perioperative and long-term results were compared with those of 202 matched patients with a standard pancreatic resection. Uni- and multivariate regression analysis were performed to identify parameters that are associated with perioperative morbidity. Long-term survival was evaluated., Results: Colon, stomach, adrenal gland, liver, hepatic or celiac artery, kidney, or small intestine were resected in 37.6%, 33.7%, 27.7%, 18.8%, 16.8%, 11.9%, and 6.9% of the 101 patients with multivisceral resection, respectively. Additional portal vein resection was performed in 20.8% of patients. Overall and surgical morbidity but not mortality was significantly increased compared with standard pancreatic resections (55.5% vs. 42.8%, 37.6 vs. 25.3%, and 3.0% vs. 1.5%, respectively). Uni- and multivariate analysis identified a long operative time and the extended multivisceral resection of 2 or more additional organs as independent risk factors for intraabdominal complications or need for relaparotomy. Median survival was comparable to that of standard pancreatic resections., Conclusions: Multivisceral resections can be performed with increased morbidity but comparable mortality and long-term prognosis as compared with standard pancreatic resections at high volume centers. Increased morbidity is related to extended multivisceral resections with a long operative time.

After weaning from PMV, patients are usually far from ready to resume normal activities. A prolonged recovery period after catastrophic illness is the rule, with multidisciplinary rehabilitation and discharge planning efforts. Following such efforts, reports of success of restorative care are institutional and population specific. That all PMV patients are not "chronically critically ill" introduces selection factors that make comparisons between institutions even more difficult. Half of the authors' patients were able to go home in past years [14], although more recently, with patients admitted more debilitated and more ill, the percent returning home has gradually declined to the low 20% range. Bagley et al [11] report discharge to home in 31% of patients weaned. Gracey et al [6,133], treating younger, postsurgical patients, have reported the highest discharge to home rate, 57%; over 70% were eventually discharged to home after first being transferred to a rehabilitation unit. On the other hand, the few reports of survival 1 or more years after discharge are in the 50% range at best (Table 2). Carson and colleagues [9] report a 23% 1-year survival in 133 PMV patients. Their premorbid functional status and age analysis showed younger and more independent patients having a better mortality (56%), and older and more dependent patients having a 95% mortality at 1 year. Nasraway et al [25] report a 1-year mortality of 50.5% in 97 patients transferred from five ICUs to multiple ECFs. Most of these patients would probably meet criteria for PMV, with median time mechanically ventilated 33 days, and 71 ventilator dependent at the time of ICU discharge. A report from 25 Vencor Hospitals [134] not included in Table 2 because weaning outcome was not reported, examines mortality and cost in patients > 65 years of age primarily referred for failure to wean from mechanical ventilation (91% of the cohort of 1619 patients.) There was a 58% in-hospital mortality by day 102 (28 days in the acute care hospital before referral, 74 days in the LTAC afterward), and a 67% mortality in postdischarge follow-up to day 180. Results of functional status studies and quality-of-life (QQL) measures, some using validated instruments, are now being reported in small series of PMV patients. These will merit consideration as important as weaning outcome, disposition, and survival data, as they accumulate to round out the treatment results in this population. Using a proprietary instrument, Carson et al [9] found 42% of 1-year survivors, that is, 8% of study patients, functionally independent at 1 year after discharge. Nasraway [25], using a single-question QQL assessment, and a validated functionality measurement, found 11.5% of his original cohort at home, breathing independently, with a "fair or better" QOL and good physical functionality. In a preliminary report from Dr. Criner's VRU, objective physical improvement was demonstrated in rehabilitation after PMV, using a functional independence measure scale [89]. A full report from the same unit, using a Sickness Impact Profile score makes it clear that PMV had no independent adverse effect on QOL several years later [135]. The 46 patients (25 of whom, with mean age 59 years, responded to the follow-up questionnaire), followed for 24 months after the catastrophic episode, scored their QOL based on their underlying chronic diseases, if any. The older patients, status postsurgical illness, predominantly cardiac surgery, rated their QOL better than younger patients with acute or chronic diseases. Similar findings have been reported in a recent ICU study, reporting QOL after prolonged intensive care [136]. Those who work to liberate PMV patients from mechanical ventilation, a satisfying end in many ways, have demonstrated that this post-ICU critical care activity is usually safe, and successful, although only in observational studies. Will multicenter studies in PMV patients liberated from mechanical ventilation yield facility benchmark, weaning outcome, and survival data that warrant continuation of these activities on a cost-per-outcome basis? That remains to be seen. Assessing and interpreting QOL and functionality findings in these patients, many with underlying chronic diseases resulting in long convalescence and rehabilitation, is a particularly important challenge. The authors are participating in a multicenter study that will yield some of these data; no doubt others will also address these questions. In the mean time, "No one in our society is willing to put Grandma out on an iceberg because she's no longer contributing. Someone needs to take care of these people" [137].

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.

When patients suffer prolonged mechanical ventilation, physicians are faced with a series of decisions beginning in the intensive care unit (ICU) and extending into a broadening spectrum of post-ICU levels of care. This article reviews current thinking and outcome data on when and how to perform the tracheostomy, as well as when and where the patient should be transferred from the ICU for continued weaning efforts or support. Decannulation after success in weaning and continuation of ventilation at home are also addressed.

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.

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.

BACKGROUND: In the intensive care unit (ICU) setting, the combination of mechanical ventilation and renal replacement therapy (RRT) has been associated with prolonged length of hospital stay, high cost of care and poor outcome. We gathered outcome data on patients who had severe renal dysfunction on transfer to our regional weaning center (RWC) for attempted weaning from prolonged mechanical ventilation (PMV). We screened the admission laboratory values of 1077 patients transferred to our RWC over an 8-year period. We reviewed the medical records of patients with serum creatinine > 2.5 mg/dl. RESULTS: Sixty-three patients met screening criteria and 40 patients were on RRT at the time of transfer. Eighteen patients had begun chronic RRT at least 2 months prior to admission to the transferring hospital for their current illness. Twenty-two patients had RRT initiated at the transferring hospital. Ten patients had RRT initiated at the RWC; eight patients had improvement or resolution of azotemia at our facility. RRT was withheld at patient/family request in five patients with progressive renal failure. None of the 50 patients who received RRT recovered renal function during treatment at our RWC. Intermittent hemodialysis was the standard RRT at the RWC. Duration of mechanical ventilation prior to transfer to the RWC was 49.7 +/- 33.5 days (mean +/- SD).Outcome of weaning attempts in the 63 patients was as follows: 13% weaned, 3% failed to wean and 84% died. These outcomes were significantly worse (P<0.001) than those in the 1014 patients whose admission serum creatinine was

Study Objective: To identify variables associated with weaning outcome in long-term ventilator-dependent patients. Using those variables, to construct models to predict weaning success and to test the accuracy of those models., Design: Retrospective medical record review., Setting: Regional weaning center (RWC)., Patients: An initial group of 421 and a subsequent group of 170 consecutive patients referred for attempted weaning after 6 weeks of mechanical ventilation., Measurements and Results: Data obtained on admission to our facility were analyzed for correlation with weaning outcome. In the initial patient group, selected variables which correlated with weaning success were alveolar-arterial oxygen pressure difference (P[A-a]O2), BUN, BUN/creatinine ratio (each with p < or = 0.001), and female gender (p = 0.04). We used these variables in logistic regression models to predict weaning success in this population. We then tested the models in the 170-patient validation group using both standard and receiver operating characteristic (ROC) curve analysis. The ROC analysis indicated 59% accuracy using P(A-a)O2 alone and 68% accuracy using all previously mentioned variables. We used data from all 565 patients with known outcome and omitted BUN/creatinine ratio to fashion a simple scoring system to predict weaning success with 70% accuracy using P(A-a)O2, BUN, and Gender--the A+B+G score., Conclusion: In patients suffering prolonged mechanical ventilation, models incorporating simple measurements allowed construction of a score to predict weaning success at our RWC.