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Background: In patients who are ventilator-dependent in the intensive care unit, inspiratory muscle training may improve inspiratory muscle strength and accelerate liberation from the ventilator, but optimal training parameters are yet to be established, and little is known about the impact of inspiratory muscle training on quality of life or dyspnoea. Thus, we sought to ascertain whether inspiratory muscle training, commenced while ventilator-dependent, would improve outcomes for patients invasively ventilated for 7 days or longer., Methods: In this randomised trial with assessor blinding and intention-to-treat analysis, 70 participants (mechanically ventilated ≥7 days) were randomised to receive once-daily supervised high-intensity inspiratory muscle training with a mechanical threshold device in addition to usual care or to receive usual care (control). Primary outcomes were inspiratory muscle strength (maximum inspiratory pressure % predicted) and endurance (fatigue resistance index) at ventilator liberation and 1 week later. Secondary outcomes included quality of life (SF-36v2, EQ-5D), dyspnoea, physical function, duration of ventilation, and in-hospital mortality., Results: Thirty-three participants were randomly allocated to the training group, and 37 to the control group. There were no statistically significant differences in strength (maximum inspiratory pressure) (95% confidence interval [CI]: -7.4 to 14.0) or endurance (fatigue resistance index) (95% CI: -0.003 to 0.436). Quality of life improved significantly more in the training group than in the control group (EQ-5D: 17.2; 95% CI: 1.3-33.0) (SF-36-PCS: 6.97; 95% CI: 1.96-12.00). Only the training group demonstrated significant reductions in dyspnoea (-1.5 at rest, -1.9 during exercise). There were no between-group differences in duration of ventilation or other measures. In-hospital mortality was higher in the control group than in the training group (9 vs 4, 24% vs 12%, p = 0.23)., Conclusions: In patients who are ventilator-dependent, mechanical threshold loading inspiratory muscle training improves quality of life and dyspnoea, even in the absence of strength improvements or acceleration of ventilator liberation., (Copyright © 2022 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Recent studies suggest that displays of unacceptable behaviour, including bullying, discrimination and harassment, between healthcare workers (HCWs) may impair job performance, and in turn, increase the frequency of medical errors, adverse events and healthcare-related complications. The objective of this systematic review was to summarise the current evidence of the impact of unacceptable behaviour occurring between HCWs on clinical performance and patient outcomes., Methods: We searched MEDLINE, Embase, PsycINFO and CINAHL from 1 January 1990 to 31 March 2021. The search results were screened by two independent reviewers and studies were included if they were original research that assessed the effects of unacceptable behaviour on clinical performance, quality of care, workplace productivity or patient outcomes. Risk of bias was assessed using tools relevant to the study design and the data were synthesised without meta-analysis., Results: From the 2559 screened studies, 36 studies were included: 22 survey-based studies, 4 qualitative studies, 3 mixed-methods studies, 4 simulation-based randomised controlled trials (RCTs) and 3 other study designs. Most survey-based studies were low quality and demonstrated that HCWs perceived a relationship between unacceptable behaviour and worse clinical performance and patient outcomes. This was supported by a smaller number of higher quality retrospective studies and RCTs. Two of four RCTs produced negative results, possibly reflecting inadequate power or study design limitations. No study demonstrated any beneficial effect of unacceptable behaviour on the study outcomes., Conclusions: Despite the mixed quality of evidence and some inconsistencies in the strengths of associations reported, the overall weight of evidence shows that unacceptable behaviour negatively affects the clinical performance of HCWs, quality of care, workplace productivity and patient outcomes. Future research should focus on the evaluation and implementation of interventions that reduce the frequency of these behaviours., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background : Inspiratory muscle training (IMT) increases inspiratory muscle strength and improves quality of life in intensive care unit (ICU) patients who have been invasively mechanically ventilated for ≥7 days. The purpose of this study was to identify which patients benefit most from IMT following weaning from mechanical ventilation. Methods : Secondary analysis of a randomized trial of supervised daily IMT in 70 patients (mean age 59 years) in a 31-bed ICU was carried out. Changes in inspiratory muscle strength (maximum inspiratory pressure, MIP) between enrolment and 2 weeks (ΔMIP) were analyzed to compare the IMT group (71% male) and the control group (58% male). Linear regression models explored which factors at baseline were associated with ΔMIP. Results : Thirty-four participants were allocated to the IMT group where baseline MIP was associated with an increase in ΔMIP, significantly different from the control group ( p = 0.025). The highest ΔMIP was associated with baseline MIP ≥ 28 cmH 2 O. In the IMT group, higher baseline quality of life (EQ5D) scores were associated with positive ΔMIP, significantly different from the control group ( p = 0.029), with largest ΔMIP for those with EQ5D ≥ 40. Conclusions : Physiotherapists should target ICU patients with moderate inspiratory muscle weakness (MIP ≥28 cmH 2 O) and moderate to high quality of life (EQ5D>40) within 48 h of ventilatory weaning as ideal candidates for IMT following prolonged mechanical ventilation.

Recent evidence of the occurrence of discrimination, bullying and sexual harassment in surgery and more generally within healthcare has led to widespread discussion about the effects of unacceptable behaviour in surgical education and practice. Despite accumulating evidence of the adverse effects of unacceptable behaviour in clinical practice, not only on health care professionals but on patient care and outcomes, many surgeons and other health care professionals continue to embrace false perceptions about appropriate professional behaviour, interactions and approaches to teaching within surgical departments and more generally within healthcare institutions. This article explores five misperceptions about unacceptable behaviour in surgical education and provides evidence that supports a change in practice., (© 2020 Royal Australasian College of Surgeons.)

Objectives: To describe a multidisciplinary approach to inspiratory muscle training (IMT) for patients in the intensive care unit (ICU)., Background: Inspiratory muscle weakness is a known consequence of prolonged mechanical ventilation, and there is emerging evidence that specific IMT can ameliorate this weakness. However, IMT is not yet standard practice in many ICUs, possibly because of the wide variety of methods reported and a lack of published practical guidelines. While the optimal parameters for IMT are yet to be established, we share our detailed methodology which has been shown to be safe in selected ventilator-dependent patients and is the only approach which has been shown to increase quality of life in ICU patients., Methods: Patients who have experienced invasive mechanical ventilation for at least 7 days can commence IMT in either the ventilator-dependent phase or when weaned from mechanical ventilation. Intensity should be prescribed based on maximum inspiratory pressure, which is measurable through the tracheostomy or endotracheal tube via the ventilator or a respiratory pressure meter. Using a removable threshold device, we recommend high-intensity training (5 sets of 6 breaths at a minimum of 50% of maximum inspiratory pressure) performed once per day, supervised by the physiotherapist, with intensity increased daily such that patients can only just complete the 6th breath in each set., Results: Using this high-intensity approach, IMT is likely to improve not only inspiratory muscle strength but also quality of life in patients recently weaned from mechanical ventilation of 7 days' duration or longer. Effective IMT requires a multidisciplinary approach to maximise feasibility, with doctors, nurses, and therapists working closely to optimise conditions for successful IMT., Conclusions: This multidisciplinary approach to implement IMT in ICU patients should assist clinicians in translating best-available evidence into practice, with the potential to enhance patient recovery., (Copyright © 2018 Australian College of Critical Care Nurses Ltd. All rights reserved.)

Background: In patients who have been mechanically ventilated, inspiratory muscles remain weak and fatigable following ventilatory weaning, which may contribute to dyspnoea and limited functional recovery. Inspiratory muscle training may improve inspiratory muscle strength and endurance following weaning, potentially improving dyspnoea and quality of life in this patient group., Methods: We conducted a randomised trial with assessor-blinding and intention-to-treat analysis. Following 48 hours of successful weaning, 70 participants (mechanically ventilated ≥7 days) were randomised to receive inspiratory muscle training once daily 5 days/week for 2 weeks in addition to usual care, or usual care (control). Primary endpoints were inspiratory muscle strength and fatigue resistance index (FRI) 2 weeks following enrolment. Secondary endpoints included dyspnoea, physical function and quality of life, post-intensive care length of stay and in-hospital mortality., Results: 34 participants were randomly allocated to the training group and 36 to control. The training group demonstrated greater improvements in inspiratory strength (training: 17%, control: 6%, mean difference: 11%, p=0.02). There were no statistically significant differences in FRI (0.03 vs 0.02, p=0.81), physical function (0.25 vs 0.25, p=0.97) or dyspnoea (-0.5 vs 0.2, p=0.22). Improvement in quality of life was greater in the training group (14% vs 2%, mean difference 12%, p=0.03). In-hospital mortality was higher in the training group (4 vs 0, 12% vs 0%, p=0.051)., Conclusions: Inspiratory muscle training following successful weaning increases inspiratory muscle strength and quality of life, but we cannot confidently rule out an associated increased risk of in-hospital mortality., Trial Registration Number: ACTRN12610001089022, results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: To describe our experience and the practical tools we have developed to facilitate early mobilization in the intensive care unit (ICU) as a multidisciplinary team., Background: Despite the evidence supporting early mobilization for improving outcomes for ICU patients, recent international point-prevalence studies reveal that few patients are mobilized in the ICU. Existing guidelines rarely address the practical issues faced by multidisciplinary ICU teams attempting to translate evidence into practice. We present a comprehensive strategy for safe mobilization utilized in our ICU, incorporating the combined skills of medical, nursing, and physiotherapy staff to achieve safe outcomes and establish a culture which prioritizes this intervention., Methods: A raft of tools and strategies are described to facilitate mobilization in ICU by the multidisciplinary team. Patients without safe unsupported sitting balance and without ≥3/5 (Oxford scale) strength in the lower limbs commence phase 1 mobilization, including training of sitting balance and use of the tilt table. Phase 2 mobilization involves supported or active weight-bearing, incorporating gait harnesses if necessary. The Plan B mnemonic guides safe multidisciplinary mobilization of invasively ventilated patients and emphasizes the importance of a clearly articulated plan in delivering this valuable treatment as a team., Discussion: These tools have been used over the past 5 years in a tertiary ICU with a very low incidence of adverse outcomes (<2%). The tools and strategies described are useful not only to guide practical implementation of early mobilization, but also in the creation of a unit culture where ICU staff prioritize early mobilization and collaborate daily to provide the best possible care., Conclusion: These practical tools allow ICU clinicians to safely and effectively implement early mobilization in critically ill patients. A genuinely multidisciplinary approach to safe mobilization in ICU is key to its success in the long term.

Objectives: To establish the inter-rater reliability of the Acute Care Index of Function (ACIF) in intensive care unit (ICU) patients and determine whether ACIF scores have predictive utility beyond ICU discharge., Background: Accurate and reliable measures of physical function are required to describe the recovery trajectory of ICU survivors. The clinimetric properties of the ACIF are yet to be established in ICU patients., Methods: Prospective observational study in a single tertiary ICU. ACIF scores were recorded independently by 2 physiotherapists across a convenience sample of 100 physiotherapy assessments, and at ICU discharge., Results: Inter-rater reliability of total ACIF scores was very strong (ICC = 0.94). ACIF <0.40 at ICU discharge predicted hospital discharge to a destination other than home (area under ROC = 0.79, 95% CI 0.64-0.89) (sensitivity 0.78)., Conclusion: The ACIF has excellent inter-rater reliability in ICU patients and scores at ICU discharge predict the likelihood of discharge home., Trial Registration: ACTRN12614001008617 (September 18 2014)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to establish whether intensive care unit (ICU) patients have impaired inspiratory muscle (IM) endurance immediately following weaning from prolonged mechanical ventilation (MV), and whether IM weakness is related to function or perceived exertion., Background: Impaired IM endurance may hinder recovery from MV, however it is unknown whether this affects patients' function or perceived exertion., Methods: Prospective observational study of 43 adult ICU patients following weaning from MV (>7 days duration). IM endurance was measured using the fatigue resistance index (FRI)., Results: IM endurance was impaired (FRI = mean 0.90, SD 0.31), with 37% scoring below 0.80. IM strength did not significantly correlate with function (r = 0.24, p = 0.12) or perceived exertion during exercise (r = -0.146, p = 0.37)., Conclusions: IM endurance is reduced in one third of patients, while IM weakness does not appear closely associated with function or perceived exertion immediately following successful weaning., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to develop consensus recommendations on safety parameters for mobilizing adult, mechanically ventilated, intensive care unit (ICU) patients., Methods: A systematic literature review was followed by a meeting of 23 multidisciplinary ICU experts to seek consensus regarding the safe mobilization of mechanically ventilated patients., Results: Safety considerations were summarized in four categories: respiratory, cardiovascular, neurological and other. Consensus was achieved on all criteria for safe mobilization, with the exception being levels of vasoactive agents. Intubation via an endotracheal tube was not a contraindication to early mobilization and a fraction of inspired oxygen less than 0.6 with a percutaneous oxygen saturation more than 90% and a respiratory rate less than 30 breaths/minute were considered safe criteria for in- and out-of-bed mobilization if there were no other contraindications. At an international meeting, 94 multidisciplinary ICU clinicians concurred with the proposed recommendations., Conclusion: Consensus recommendations regarding safety criteria for mobilization of adult, mechanically ventilated patients in the ICU have the potential to guide ICU rehabilitation whilst minimizing the risk of adverse events.

Background: Mechanical ventilation of intensive care patients results in inspiratory muscle weakness. Inspiratory muscle training may be useful, but no studies have specifically described the physiological response to training., Research Questions: Is inspiratory muscle training with a threshold device safe in selected ventilator-dependent patients? Does inspiratory muscle strength increase with high-intensity inspiratory muscle training in ventilator-dependent patients?, Design: Prospective cohort study of 10 medically stable ventilator-dependent adult patients., Setting: Tertiary adult intensive care unit., Methods: Inspiratory muscle training 5-6 days per week with a threshold device attached to the tracheostomy without supplemental oxygen., Outcome Measures: Physiological response to training (heart rate, mean arterial pressure, oxygen saturation and respiratory rate), adverse events, training pressures., Results: No adverse events were recorded in 195 sessions studied. For each patient's second training session, no significant changes in heart rate (Mean Difference 1.3 bpm, 95% CI -2.7 to 5.3), mean arterial pressure (Mean Difference -0.9 mmHg, 95% CI -6.4 to 4.6), respiratory rate (Mean Difference 1.2 bpm, 95% CI -1.1 to 3.5 bpm) or oxygen saturation (Mean Difference 1.2%, 95% CI -0.6 to 3.0) were detected Training pressures increased significantly (Mean Difference 18.6 cmH(2)O, 95% CI 11.8-25.3)., Conclusion: Threshold-based inspiratory muscle training can be delivered safely in selected ventilator-dependent patients without supplemental oxygen. Inspiratory muscle training is associated with increased muscle strength, which may assist ventilatory weaning., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: Inspiratory muscle weakness is a known consequence of mechanical ventilation and a potential contributor to difficulty in weaning from ventilatory support. Inspiratory muscle training (IMT) reduces the weaning period and increases the likelihood of successful weaning in some patients. However, it is not known how this training affects the residual inspiratory muscle fatigability following successful weaning nor patients' quality of life or functional outcomes., Methods and Analysis: This dual centre study includes two concurrent randomised controlled trials of IMT in adult patients who are either currently ventilator-dependent (>7 days) (n=70) or have been recently weaned from mechanical ventilation (>7 days) in the past week (n=70). Subjects will be stable, alert and able to actively participate and provide consent. There will be concealed allocation to either treatment (IMT) or usual physiotherapy (including deep breathing exercises without a resistance device). Primary outcomes are inspiratory muscle fatigue resistance and maximum inspiratory pressures. Secondary outcomes are quality of life (Short Form-36v2, EQ-5D), functional status (Acute Care Index of Function), rate of perceived exertion (Borg Scale), intensive care length of stay (days), post intensive care length of stay (days), rate of reintubation (%) and duration of ventilation (days)., Ethics and Dissemination: Ethics approval has been obtained from relevant institutions, and results will be published with a view to influencing physiotherapy practice in the management of long-term ventilator-dependent patients to accelerate weaning and optimise rehabilitation outcomes., Trial Registration Number: ACTRN12610001089022.

Purpose: Recently there has been increased interest in early mobilization of critically ill patients. Proposed benefits include improvements in respiratory function, muscle wasting, intensive care unit (ICU), and hospital length of stay. We studied the frequency of early mobilization in our intensive care unit in order to identify barriers to early mobilization., Methods: A 4-week prospective audit of 106 patients admitted to a mixed medical-surgical tertiary ICU (mean age 60 ± 20 years, mean APACHE II score 14.7 ± 7.8) was performed. Outcome measures included number of patient days mobilized, type of mobilization, adverse events, and reasons for inability to mobilize., Results: Patients were mobilized on 176 (54%) of 327 patient days. Adverse events occurred in 2 of 176 mobilization episodes (1.1%). In 71 (47%) of the 151 patient days where mobilization did not occur, potentially avoidable factors were identified, including vascular access devices sited in the femoral region, timing of procedures and agitation or reduced level of consciousness., Conclusions: Critically ill patients can be safely mobilized for much of their ICU stay. Interventions that may allow more patients to mobilize include: changing the site of vascular catheters, careful scheduling of procedures, and improved sedation management.

Respiratory muscle dysfunction is associated with prolonged and difficult weaning from mechanical ventilation. This dysfunction in ventilator-dependent patients is multifactorial: there is evidence that inspiratory muscle weakness is partially explained by disuse atrophy secondary to ventilation, and positive end-expiratory pressure can further reduce muscle strength by negatively shifting the length-tension curve of the diaphragm. Polyneuropathy is also likely to contribute to apparent muscle weakness in critically ill patients, and nutritional and pharmaceutical effects may further compound muscle weakness. Moreover, psychological influences, including anxiety, may contribute to difficulty in weaning. There is recent evidence that inspiratory muscle training is safe and feasible in selected ventilator-dependent patients, and that this training can reduce the weaning period and improve overall weaning success rates. Extrapolating from evidence in sports medicine, as well as the known effects of inspiratory muscle training in chronic lung disease, a theoretical model is proposed to describe how inspiratory muscle training enhances weaning and recovery from mechanical ventilation. Possible mechanisms include increased protein synthesis (both Type 1 and Type 2 muscle fibres), enhanced limb perfusion via dampening of a sympathetically-mediated metaboreflex, reduced lactate levels and modulation of the perception of exertion, resulting in less dyspnoea and enhanced exercise capacity.

This report describes the use of specific inspiratory muscle training to enhance weaning from mechanical ventilation in a patient who had failed conventional weaning strategies. A 79-year-old man remained ventilator-dependent 17 days following laparotomy. A program of daily inspiratory muscle training was initiated. The mean training threshold increased progressively during the program and simultaneously the periods of unassisted breathing achieved gradually increased. By day 27, mechanical ventilation was no longer required. Inspiratory muscle training can be implemented effectively in the difficult to wean patient and should be considered for patients who have failed conventional weaning strategies.

Objective: To determine the safety and efficacy of an intensive insulin regimen compared with a conventional insulin regimen in general intensive care unit patients., Methods: A phase II, randomised controlled trial was conducted in 70 critically ill patients in a closed multidisciplinary ICU of a university-affiliated tertiary hospital. We assessed patient characteristics at baseline. Trial process measures included number of blood glucose measurements per day and number in target range, type and quantity of caloric intake, patient outcome and insulin dosing. The primary outcome was the median blood glucose concentration. Secondary outcome measures were incidence of hypoglycaemia (blood glucose level < 2.2 mmol/L), clinical sequelae of hypoglycaemia and hospital mortality., Results: Thirty-five patients were randomised to each of the two groups. More blood glucose samples were taken per day in the intensive insulin group (16 versus 9), but the number of samples in the normoglycaemic range was 48.5%, compared with 79.8% within the target glucose range in the conventional insulin group. The median (interquartile range) blood glucose concentrations in the intensive and conventional insulin therapy groups were 5.4 (5.1-5.7) mmol/L and 7.9 (7.2-9.0) mmol/L, respectively (difference, 2.5 mmol/L; P < 0.0001). Five patients (14.3%) in the intensive insulin therapy group became hypoglycaemic versus none in the conventional insulin therapy group. There were no detected clinical sequelae of hypoglycaemia., Conclusion: The intensive insulin regimen was effective in achieving the target blood glucose concentration, with clear separation from the conventional insulin regimen. Although the incidence of hypoglycaemia was increased, there was no detectable harm.

An acute cardiac tamponade from any cause may result in rapid deterioration of hepatic function in a previously healthy patient. We describe a case of an acute ascending aortic dissection that presented as acute hepatic failure, due to an acute cardiac tamponade and severe right heart failure. The differential diagnosis of the aetiology of acute liver failure is extensive and includes poisonings, vascular obstruction and sepsis, particularly on the background of decompensated liver disease. Many of these conditions are associated with hypotension. The acute presentation in our patient, combined with the lack of a characteristic history delayed the diagnosis of a proximal (type A) dissection with tamponade and subsequent hepatic failure. Severe right-sided heart failure as a result of conditions such as cardiac tamponade should be excluded in patients presenting with acute hepatic failure of unknown aetiology.

Objective: The aim of the present study was to examine the relationship between serious arrhythmias in patients with psychotropic drug overdose and electrocardiography (ECG) findings that have been suggested previously to predict this complication., Methods: Thirty-nine patients with serious arrhythmias (ventricular tachycardia, supraventricular tachycardia or cardiac arrest) after tricyclic antidepressant overdose or thioridazine overdose were compared with 117 controls with clinically significant overdose matched to each case for the drug ingested. These patients with psychotropic drug overdose had presented for treatment to the Department of Clinical Toxicology, Newcastle and to the Princess Alexandra Hospital, Brisbane. The heart rate, the QRS width, the QTc and QT intervals, the QT dispersion, and the R wave and R/S ratios in aVR on the initial ECGs were compared in cases and controls., Results: The cases had taken dothiepin (16 patients), doxepin (six patients), thioridazine (five patients), amitriptyline (five patients), nortriptyline (three patients), imipramine (one patient) and a combination of dothiepin and thioridazine (three patients). In 20 of the 39 patients with arrhythmias, the arrhythmia had been a presumed ventricular tachycardia. Of the other 19 patients, 15 patients had a supraventricular tachycardia, two patients had cardiac arrests (one asystole, one without ECG monitoring) and two patients had insufficient data recorded to make classification of the arrhythmias possible. The QRS was >/= 100 ms in 82% of cases but also in 76% of controls. QRS >/= 160 ms had a sensitivity of only 13% and occurred in 2% of controls. QRS > 120 ms, QTc > 500 and the R/S ratio in aVR appeared to have a stronger association with the occurrence of arrhythmia: QRS > 120 ms (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.46-8.68), QTc > 500 (OR, 3.07; 95% CI, 1.33-7.07), and R/S ratio in aVR > 0.7 (OR, 16; 95% CI, 3.47-74). Excluding thioridazine overdoses and performing the analysis for tricyclic antidepressant overdoses alone gave increased odds ratios for QRS > 120 ms (OR, 4.83; 95% CI, 1.73-13.5) and QTc > 500 (OR, 4.5; 95% CI, 1.56-13) but had little effect on that for the R/S ratio in aVR > 0.7 (OR, 14.5; 95% CI, 3.10-68)., Conclusion: ECG measurements were generally weakly related to the occurrence of arrhythmia and should not be used as the sole criteria for risk assessment in tricyclic antidepressant overdose. The frequently recommended practice of using either QRS >/= 100 ms or QRS >/= 160 ms to predict arrhythmias is not supported by our study. R/S ratio in aVR > 0.7 was most strongly related to arrhythmia but had estimated positive and negative predictive values of only 41% and 95%, respectively. The use of these specific predictors in other drug overdoses is not recommended without specific studies.

Renal osmolyte concentrations are reduced during reflow following ischemia. Osmolyte decreases may follow oxygen depletion or loss of extracellular osmolality in the medulla. Image-guided volume-localized magnetic resonance (MR) microspectroscopy was used to monitor regional osmolytes during hyposmotic shock and hypoxia in the intact rat kidney. Alternate spectra were acquired from 24-microl voxels in cortex and medulla of the isolated perfused kidney. There was a progressive decrease in the combined betaine-glycerophosphorylcholine (GPC) peak intensity of 21% in cortex and 35% in medulla of normoxic kidneys between 60 and 160 min after commencing perfusion. Hypoxia had no significant effect on the betaine-GPC peak intensity in cortex or medulla, despite a dramatic reduction in tubular sodium, potassium, and water reabsorption. The results suggest that cortical and medullary intracellular osmolyte concentrations depend on osmotically regulated channels that are insensitive to oxygen and dissociated from the oxygen-dependent parameters of renal function, the fractional excretion of sodium, the fractional excretion of potassium, and urine-to-plasma inulin concentration ratio.

Volume-localized proton nuclear magnetic resonance spectroscopy was used as an assay of regional biochemistry in the isolated perfused rat kidney. This model eliminated artifacts caused by respiratory and cardiac motion experienced in vivo. Immersion of the kidney under its venous effluent reduced the susceptibility artifacts evoked by tissue-air interfaces. The rapid acquisition with relaxation enhancement imaging sequence was used for scout imaging. This gave excellent spatial resolution of the cortex, outer medulla, and inner medulla. Spectra were then acquired in 10 minutes using the volume-selective multipulse spectroscopy sequence from voxels with a volume of approximately 24 microL located within the cortical or medullary regions. Spectral peaks were assigned by the addition of known compounds to the perfusion medium and by comparison with spectra of protein-free extracts of cortex and medulla. The medullary region spectra were characterized by signals from the osmolytes betaine, glycerophosphorylcholine, and inositol. The spectra from the cortex were more complex and contained lesser contributions from osmolytes.