Intra-operative protective mechanical ventilation in lung transplantation: a randomised, controlled trial.

Primary graft dysfunction occurs in up to 25% of patients after lung transplantation. Contributing factors include ventilator-induced lung injury, cardiopulmonary bypass, ischaemia-reperfusion injury and excessive fluid administration. We evaluated the feasibility, safety and efficacy of an open-lung protective ventilation strategy aimed at reducing ventilator-induced lung injury. We enrolled adult patients scheduled to undergo bilateral sequential lung transplantation, and randomly assigned them to either a control group (volume-controlled ventilation with 5 cmH2 O, positive end-expiratory pressure, low tidal volumes (two-lung ventilation 6 ml.kg-1 , one-lung ventilation 4 ml.kg-1 )) or an alveolar recruitment group (regular step-wise positive end-expiratory pressure-based alveolar recruitment manoeuvres, pressure-controlled ventilation set at 16 cmH2 O with 10 cmH2 O positive end-expiratory pressure). Ventilation strategies were commenced from reperfusion of the first lung allograft and continued for the duration of surgery. Regular PaO2 /FI O2 ratios were calculated and venous blood samples collected for inflammatory marker evaluation during the procedure and for the first 24 h of intensive care stay. The primary end-point was the PaO2 /FI O2 ratio at 24 h after first lung reperfusion. Thirty adult patients were studied. The primary outcome was not different between groups (mean (SD) PaO2 /FI O2 ratio control group 340 (111) vs. alveolar recruitment group 404 (153); adjusted p = 0.26). Patients in the control group had poorer mean (SD) PaO2 /FI O2 ratios at the end of the surgical procedure and a longer median (IQR [range]) time to tracheal extubation compared with the alveolar recruitment group (308 (144) vs. 402 (154) (p = 0.03) and 18 (10-27 [5-468]) h vs. 15 (11-36 [5-115]) h (p = 0.01), respectively). An open-lung protective ventilation strategy during surgery for lung transplantation is feasible, safe and achieves favourable ventilation parameters.

Clinical benefits of a specialised clinic for hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac condition, with a range of investigation and management options available. Recent research has recommended management within multidisciplinary-dedicated HCM centres. AIM: To assess the clinical impact of attendance at a specialised clinic on the management of HCM. METHODS: A retrospective study of patients attending the HCM Clinic @ The Alfred during the first 2 years of operation was performed. Outcome measures comprised improvements in management of HCM as a result of attending the clinic including risk stratification and further investigations, medication changes, referral for implantable cardioverter-defibrillators (ICD) and septal reduction therapy, and screening of first-degree relatives (FDR). RESULTS: Following specialised clinic attendance, there was an increase in patients investigated with 24-h Holter monitoring by 39%, stress echocardiography by 21% and cardiac magnetic resonance imaging by 70%. Medications were optimised in 47% of patients. Six per cent of patients underwent ICD implantation and 13% underwent septal myectomy. Seventy new FDR were screened identifying 10 new cases of HCM. CONCLUSIONS: Attendance at our specialised HCM clinic leads to facilitation of cardiac investigations, optimisation of medical therapy, streamlining of referrals for ICD implantation and septal reduction therapy, and improved family screening. Referral to a specialised clinic offering comprehensive management should be considered for all patients with HCM.

Early lung transplantation success utilizing controlled donation after cardiac death donors.

Donation-after cardiac death (DCD) donor organs have potential to significantly alleviate the shortage of transplantable lungs. However, only limited data so far describes DCD lung transplantation (LTx) techniques and results. This study aims to describe the Alfred Hospital's early and intermediate outcomes following DCD donor LTx. Following careful experimentation and consultation DCD guidelines were created to utilize Maastricht category III lung donors from either the ICU or operating room(OR), with a warm ischemic time(WIT) of <60 min. Between May 2006 and December 2007, 22 referred DCD donors led to 11 attempted retrievals after withdrawal, resulting in 8 actual bilateral LTx (2 donors did not arrest in prescribed period and 1 donor had nonacceptable lungs). ICU WIT = 38.4 min (range 20-54, OR WIT = 12.7 min (11-15), p < 0.05. Post-LTx, 1 pulmonary hypertensive patient required ECMO for PGD3. The mean group pO2/FiO2 ratio at 24 hours was 307.7 (240-507) with an ICU stay of 9.5 days (2-21) and ward stay of 21.5 days (11-76). All 8 survive at a mean of 311 days (10-573) with good performance status and lung function. In conclusion, the use of Maastricht category III lungs for human LTx is associated with acceptable early clinical outcomes.

Association between primary graft dysfunction among lung, kidney and heart recipients from the same multiorgan donor.

Even organs from an ideal donor will occasionally develop primary graft dysfunction (PGD) causing a significant morbidity and mortality after transplantation. It is likely that this situation represents subtle undetectable levels of ongoing donor organ dysfunction. The aim of this study is to investigate the association of PGD between lung, kidney and heart recipients from the one donor. From 202 multiorgan donors, contributed 231 consecutive lung transplants at the Alfred Hospital, 378 kidney and 114 heart transplants were subsequently performed at multiple centers across Australia and New Zealand. Eight hundred seventy-five organs were used for 723 transplants. The incidence of PGD after lung, kidney and heart transplants was 20% (47/231), 24% (92/378) and 20% (23/114), respectively. In paired single organ recipients, PGD in one of the pair was a significant risk factor for the development of PGD in the other [lung: odds ratio = 5.63 (1.72-18.43), p = 0.004; kidney: odds ratio = 3.19 (1.90-5.35), p < 0.0001]. In multivariate analysis, same donor heart PGD [3.37 (1.19-9.50), p = 0.02] was an independent risk factor for lung PGD and same donor lung PGD was significant risk factor for kidney PGD [1.94 (1.01-3.73), p = 0.04], if the PGD status of the paired kidney was not known. There was a significant association for the development of PGD across different organs transplanted from the same donor.

Glycosaminoglycan synthesis and structure as targets for the prevention of calcific aortic valve disease.

Calcific aortic valve disease is frequently driven by ageing and the obesity-associated metabolic syndrome, and the increasing impact of these factors indicates that valve disease will become a cardiovascular disease of considerable significance. This disease is now thought to be an active cell-based disease process, which may therefore be amenable to therapeutic intervention. Some similarities are apparent with atherosclerosis. The accumulation of lipid, possibly by retention by proteoglycans and the attraction of inflammatory cells by hyaluronan, may be common to the early stages of both pathologies. The synthesis and structure of glycosaminoglycans, proteoglycans, and hyaluronan are exquisitely regulated, and the signalling pathways controlling these processes may provide tissue-specific opportunities for concomitant prevention of atherosclerosis and calcific aortic valve disease.

Interhospital comparisons of coronary artery bypass graft surgical site infection rates differ if donor sites are excluded.

The advent of public reporting of hospital-acquired infection rates has sparked ongoing discussion about the most appropriate surveillance data to present. When we used different numerators to calculate rates of surgical site infection following coronary artery bypass graft surgery, we found that some hospitals' rates and their rankings were notably affected.

Surgical correction of posterior leaflet tethering in ischemic mitral regurgitation.

Ischemic mitral regurgitation is a common complication in ischemic heart disease. It is generally accepted that intervention for the mitral valve is required if there is moderate to severe regurgitation. Generally, this would involve the placement of an annuloplasty ring or band to cinch down the dilated posterior annulus. More recently, attention has been drawn to the common problem of posterior leaflet tethering in these ischemic patients and the need to specifically address this pathology. A novel method has recently been described whereby the posteromedial papillary muscle is hitched up toward the annulus by a suture and then supported with a partially flexible annuloplasty ring. The purpose of this report is to show that this technique is easily performed and reproducible in other centres, and that it produces good short to medium term results. The report details the results achieved in six consecutive patients with at least moderate mitral regurgitation and posterior leaflet tethering.

Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI.

Essentials Relationship of acquired von Willebrand disease (VWD) and platelet dysfunction is explored. Patients with ventricular assist devices and on extracorporeal membrane oxygenation are investigated. Acquired VWD and platelet receptor shedding is demonstrated in the majority of patients. Loss of platelet adhesion receptors glycoprotein (GP) Ibα and GPVI may increase bleeding risk. SUMMARY: Background Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are associated with bleeding that is not fully explained by anticoagulant or antiplatelet use. Exposure of platelets to elevated shear in vitro leads to increased shedding. Objectives To investigate whether loss of platelet receptors occurs in vivo, and the relationship with acquired von Willebrand syndrome (AVWS). Methods Platelet counts, coagulation tests and von Willebrand factor (VWF) analyses were performed on samples from 21 continuous flow VAD (CF-VAD), 20 ECMO, 12 heart failure and seven aortic stenosis patients. Levels of platelet receptors were measured by flow cytometry or ELISA. Results The loss of high molecular weight VWF multimers was observed in 18 of 19 CF-VAD and 14 of 20 ECMO patients, consistent with AVWS. Platelet receptor shedding was demonstrated by elevated soluble glycoprotein (GP) VI levels in plasma and significantly reduced surface GPIbα and GPVI levels in CF-VAD and ECMO patients as compared with healthy donors. Platelet receptor levels were also significantly reduced in heart failure patients. Conclusions These data link AVWS and increased platelet receptor shedding in patients with CF-VADs or ECMO for the first time. Loss of the platelet surface receptors GPIbα and GPVI in heart failure, CF-VAD and ECMO patients may contribute to ablated platelet adhesion/activation, and limit thrombus formation under high/pathologic shear conditions.

A procedural check list for pleural decompression and intercostal catheter insertion for adult major trauma.

BACKGROUND: Intercostal catheter (ICC) insertion is the standard pleural decompression and drainage technique for blunt and penetrating traumatic injury. Potentially high complication rates are associated with the procedure, with the literature quoting over 20% in some cases (1-4). Empyema in particular is a serious complication. Risk adverse industries such as the airline industry and military services regularly employ checklists to standardise performance and decrease human errors. The use of checklists in medical practice is exemplified by introduction of the WHO Surgical Safety checklist. METHODS: The Alfred Hospital in Melbourne, Australia is an Adult Level 1 Trauma Centre. In August 2009 The Alfred Trauma Service introduced an evidence-based checklist system for the insertion of ICCs, combined with standardised formal training for resident medical staff, in an attempt to minimise the incidence of ICC related empyema. RESULTS: Between January 2003 and July 2009 the incidence of empyema was 1.44% (29 in 2009 insertions). This decreased to 0.57% between August 2009 and December 2011 (6 in 1060 insertions) when the measures described above were introduced [p=0.038 Fisher's exact test, 2-tailed]. CONCLUSION: Quality control checklists - such as the ICC checklist described - are a sensible and functional means to standardise practice, to decrease procedural error and to reduce complication rates during trauma resuscitation.

A comparison of amiodarone and digoxin for treatment of supraventricular arrhythmias after cardiac surgery.

Despite the widespread use of amiodarone in non-surgical patients, its role in the management of supraventricular tachyarrhythmias after cardiac surgery is not clear. We set out to compare the relative efficacy of amiodarone and digoxin in the management of atrial fibrillation and flutter in the early postoperative period. This prospective randomised trial comprised 30 patients, previously in sinus rhythm, who developed sustained atrial fibrillation or flutter following myocardial revascularisation, valve surgery or combined procedures. Amiodarone was administered as an intravenous loading dose followed by a continuous infusion. Digoxin was given as an intravenous loading dose followed by oral maintenance therapy. Electrocardiographic and haemodynamic monitoring was continued for 24 h after the commencement of treatment. There was a marked reduction in heart rate in both groups, mainly in the first 6 h, from 146 to 89 beats per minute in the amiodarone group and from 144 to 95 in the digoxin group. At the end of the 24 h, one of the 15 patients in the amiodarone group and 3 of the 15 patients in the digoxin group remained in atrial fibrillation. No patient in either group developed adverse reactions. We conclude that intravenous amiodarone therapy is safe and at least as effective as digoxin in the initial management of arrhythmias after cardiac surgery.

Postoperative radial artery angiography for coronary artery bypass surgery.

OBJECTIVE: To compare radial artery (RA) patency with internal mammary artery (IMA) patency for coronary artery bypass surgery in our early experience. METHODS: Symptomatic as well as asymptomatic patients with > or =1 RA coronary graft underwent postoperative angiography. Each anastomosis was considered separately. A string sign referred to a diffusely narrowed conduit, which did not fill the grafted coronary artery, as well as all occluded conduits. The raw value of P was adjusted for the testing of multiple hypotheses (P'). The patency data for each conduit was divided into two parts. 'Cut-off' stenosis for a conduit was the lowest dividing coronary stenosis at which a difference in patency rate with P< or =0.05 occurred. RESULTS: One-hundred-and-twenty-nine patients had 137 radial arteries and 157 angiograms. Only the most recent angiogram was analyzed for each patient at 13+/-0.7 months (n=129). Overall patency for arterial conduit 91% (n=404) was not different from venous conduit 91% (n=42) and patency for RA 90% (n=226) was not different from IMA 92% (n=178), (P'=0.999). Cut-off stenosis for RA was 70% and IMA was 40%. Patent arterial conduit had a mean coronary stenosis of 85% and non-patent conduit 64%, (P'<0.001). Right coronary territory patency was 82 vs. 94% for other territories (P'=0.022). No overall differences in patency were noted for patients with sequential anastomoses, symptoms or coronary disease at the anastomosis at the time of surgery. Reversible ischaemia was detected in the distribution of only two of 14 string signs in patients undergoing sestamibi exercise protocol following angiogram. CONCLUSION: There were no differences in patency between radial artery and internal mammary artery at 13 months post-operative. Lower coronary stenosis and right coronary territory predicted lower patency. The clinical importance of a string sign remains to be determined.

Lung transplantation as rescue therapy in patients too sick to be discharged from acute care.

BACKGROUND: There is an increasing demand for lung transplantation in patients in advanced respiratory failure. Although many of these patients do not require mechanical ventilation or extracorporeal membrane oxygenation, an increasing number are critically ill. In this single-center study, we have analyzed our experience with lung transplantation in subjects who were inpatients at the time of their transplant and not expected to survive to discharge. METHODS: Between July 2006 and March 2012, we performed 274 bilateral sequential lung transplants and 34 single-lung transplants. Twenty-six patients who were inpatients at the time of their transplant, and were not expected to survive to hospital discharge, formed the inpatient group in this retrospective review. The remaining 281 outpatient lung transplant patients formed the comparison group. RESULTS: The inpatient group spent significantly fewer days on the waiting list compared to the outpatient group. Postoperative survival was significantly poorer in the inpatient group compared to the outpatient group (P = .001), and this was most noticeable in the first 90 days. There was no significant difference in survival between the inpatient transplant cohort and a historically comparable wait list cohort (P = .614). CONCLUSION: Lung transplantation in critically ill inpatients, although associated with a survival advantage compared to not transplanting them, does give poorer survival results compared to postoperative survival in outpatient patients.

Donor brain death time and impact on outcomes in heart transplantation.

INTRODUCTION: Although the early effects of brain death on the organ donor are well described, there is a paucity of information on the impact of donor brain death on the transplanted recipient's heart in both the short and long term. The few studies published report conflicting results. The aim of this article was to undertake a retrospective exploratory study examining the impact of brain death in the donor on recipient outcomes with respect to the cardiac allograft, specifically looking at primary graft failure (PGF), postoperative rejection, and survival. METHODS: A total of 215 consecutive orthotopic heart transplants performed between June 2001 and March 2011 were included in this retrospective exploratory analysis. RESULTS: Brain death time had no association with rejection-free period or mortality in this study cohort. Use of intra-aortic balloon pump support after donor allograft implantation (assessed as an indicator of PGF) was significantly associated with brain death time (odds ratio 0.998 [95% confidence interval 0.997-0.999]; P = .023) on univariate analysis with longer brain death time associated with a lower incidence of PGF. A strong correlation between brain death time and hypoxia inducible factor 1α enzyme activity in donor atrial tissue was found (r = .56; P = .002). CONCLUSION: This study indicates that there is an association between brain death time and PGF. A longer interval from brain death may give the donor heart more time to recover from the catecholamine storm. This may have implications for donation after circulatory death donor hearts, which have not been subjected to this catecholamine storm and may potentially be less likely to suffer PGF as a result.

Impact of warm ischemia time on survival after heart transplantation.

BACKGROUND: There is little data available on the specific effects of warm ischemia time (WIT) as opposed to cold ischemia or storage time. With current research endeavors focusing on warm continuous perfusion, storage of donor hearts, and utilization of hearts from non-heart-beating donors, the impact of WIT on outcomes is increasingly relevant. The aim of this study was to analyze our results in cardiac transplantation with specific focus on the impact of WIT. METHODS: A retrospective review of 206 patients who underwent orthotopic heart transplantation at our institution between June 2001 and November 2010 was performed. Donor, recipient, and operative factors were analyzed. The main outcome variables were all cause mortality, survival, and primary graft failure. RESULTS: WIT of >80 minutes was associated with reduced survival compared with a shorter WIT of <60 minutes. Multivariate analysis showed increasing donor age to be the most significant variable associated with increased risk of mortality (hazard ratio 1.04; P = .004) per year of increasing donor age. CONCLUSIONS: This study has demonstrated a reduced survival in heart transplant recipients with increased WIT. This finding may be of particular relevance to potential future heart transplantation using organs procured from non-heart-beating donors.

Pleural decompression and drainage during trauma reception and resuscitation.

This review examines pleural decompression and drainage during initial hospital adult trauma reception and resuscitation, when it is indicated for haemodynamically unstable patients with signs of pneumothorax or haemothorax. The relevant historical background, techniques, complications and current controversies are highlighted. Key findings of this review are that: 1. Needle thoracocentesis is an unreliable means of decompressing the chest of an unstable patient and should only be used as a technique of last resort. 2. Blunt dissection and digital decompression through the pleura is the essential first step for pleural decompression, as decompression of the pleural space is a primary goal during reception of the haemodynamically unstable patient with a haemothorax or pneumothorax. Drainage and insertion of a chest tube is a secondary priority. 3. Techniques to prevent tube thoracostomy (TT) complications include aseptic technique, avoidance of trocars, digital exploration of the insertion site and guidance of the tube posteriorly and superiorly during insertion. 4. Whenever possible, blunt thoracic trauma patients should undergo definitive CT imaging after TT to check for appropriate tube position.

Spontaneous resolution of multiple coronary aneurysms complicating drug eluting stent implantation.

Recent reports of coronary aneurysm formation after drug eluting stent implantation have emerged. Although various treatment modalities have been proposed, minimal data is available relating to their natural history and optimal management. We present a case of aneurysm formation in the left anterior descending and right coronary arteries after stenting with paclitaxel-eluting stents. Coronary bypass grafting of the left anterior descending and circumflex coronary arteries was subsequently required. Repeat angiography (16 months later) showed complete resolution of both coronary aneurysms. Spontaneous resolution of potentially drug eluting stent-related coronary aneurysms is documented. This phenomenon may have therapeutic implications.

Treatment of polypharmacy overdose with multimodality extracorporeal life support.

A 45-year-old woman presented to the emergency department of a tertiary referral hospital after taking an overdose of verapamil, doxepin, quetiapine, diazepam, temazepam, and clonazepam. She rapidly developed shock refractory to pharmacological support and was placed on percutaneous venoarterial extracorporeal membrane oxygenation (ECMO). She had a severe metabolic acidosis from a combination of shock and drug intoxication that improved with continuous venovenous haemodialysis. Forty-eight hours after presentation, while still on ECMO, the patient had complete cardiac standstill for three and a half hours, attributable to slow-release verapamil, that resolved after the commencement of plasmapheresis. The role of plasmapheresis in verapamil overdose requires further study.