Sleep in critically ill, mechanically ventilated patients with severe sepsis or COPD.

BACKGROUND: The standard method for scoring polysomnographic (PSG) sleep is insufficient in the intensive care unit (ICU). A modified classification has been proposed, but has not been tested in specific groups of ICU patients. We aimed firstly to (1) use the modified classification to describe sleep in two groups of ICU patients: a severe sepsis group and a chronic obstructive pulmonary disease (COPD) group, and (2) to compare sleep stage distribution in the groups; secondly to compare the PSG findings with nurses' sleep evaluation. METHODS: Non-sedated mechanically ventilated patients with severe sepsis or COPD completed up to 20-hours PSG recording in each patient. A modified classification for scoring sleep in ICU was used for scoring the PSGs. Sleep assessment by nurses was done at 15 minutes intervals. RESULTS: We included 16 patients with severe sepsis and 17 patients with COPD. Half of the patients in the severe sepsis group and 59% in the COPD group had atypical sleep. We found significantly different sleep stage distribution in the two groups, with the COPD group having a higher proportion of atypical sleep (54.4% vs 48.7%, P < .0001). No correlation between nurse sleep assessment and PSG was found in cases of atypical sleep (P < .0001). CONCLUSION: Normal PSG sleep characteristics as defined by standard classification are absent in many conscious, non-sedated critically ill patients on mechanical ventilation. Nurse sleep evaluation does not correlate with PSG if atypical sleep is present in the PSG, which limits the reliability of subjective sleep assessment in this patient population.

Patients' opinions on outcomes following critical illness.

BACKGROUND: Our aim was to explore which outcomes are most important to patients following ICU-discharge, and to explore whether intensive care unit (ICU)-nurses and anesthesiologists are aware of patients' priorities. METHODS: First, interviews with adult ICU-survivors were conducted until data saturation was achieved (10 interviews), and six areas with 36 items were identified. Second, interviews with another eight ICU-survivors were conducted, narrowing the list to 20. Finally, patients (inclusion criteria: consecutive adults, medical and surgical, ICU-admission > 5 days, 2-8 months post-ICU discharge) rated the items, as did ICU-nurses and anesthesiologists. RESULTS: A total of 32 patients participated (44% women, medians: age 70.5, time since discharge 179 days, length of stay in ICU 9 days, APACHEII 19.5). The three most important outcomes defined by patients were: lack of physical strength, fatigue, and decreased walking distance. The top three for ICU-nurses (54 participants) were: fatigue, difficulties concentrating, sadness/depression, and for anesthesiologists (17 participants): fatigue, difficulties in activities of daily living, and lack of physical strength. CONCLUSION: Patients chose lack of physical strength, fatigue, and decreased walking distance as the three most important outcomes following critical illness. Physicians had a higher focus on these physical impairments than ICU-nurses.

A randomized trial of automated intermittent ropivacaine administration vs. continuous infusion in an interscalene catheter.

BACKGROUND: Ultrasound-guided interscalene nerve block with ropivacaine as local anesthetic agent given as boluses or continuous infusion is the preferred pain management after major shoulder surgery. The use of automated intermittent boluses has been shown to be superior to continuous infusion in sciatic and epidural nerve block. HYPOTHESIS: Automated intermittent boluses reduce pain after major shoulder surgery. METHODS: Seventy patients aged 18-75 years, scheduled for major shoulder surgery under general anesthesia with interscalene nerve block were included in this randomized controlled trial. Patients were allocated to either automated intermittent boluses with 16 mg ropivacaine every 2 h combined with patient-controlled administration or to a conventional regimen of continuous infusion of 8 mg/h (4 ml/h) of ropivacaine combined with patient controlled administration (2 ml, lockout time 30 min). Pain (Visual Analog Scale, VAS) was assessed every 8 h postoperatively. RESULTS: Fifty-seven patients completed the study, 29 in the continuous infusion group and 28 in the automated intermittent bolus group. Shoulder arthroplasty was performed in 49 (86%) of the cases. There were no significant differences in VAS score from 8 to 48 h post-operatively. No significant difference in opioid usage was observed. The automated intermittent bolus group reported significantly less force on coughing and more hoarseness. A significantly lower volume of ropivacaine was used in the automated intermittent bolus group. CONCLUSION: Automated intermittent boluses did not reduce pain or rescue opioid consumption compared with continuous infusion of ropivacaine. The automated intermittent bolus group had significantly less force on coughing and more hoarseness.

Termination of pre-hospital resuscitation by anaesthesiologists - causes and consequences. A retrospective study.

AIM: Differentiating between a newly deceased patient and the lifeless patient in whom immediate resuscitation is required may be facilitated by a pre-hospital anaesthesiologist. The purpose of our study was to investigate to what extent and why the pre-hospital anaesthesiologist pronounced life extinct in situations where an emergency medical technician (EMT) would have been required to resuscitate. METHODS: All lifeless patients seen pre-hospitally by the anaesthesiologist-manned Mobile Emergency Care Unit in Odense, Denmark, from 2010 to 2014 were retrospectively studied. RESULTS: Of 17 035 contacts, 1275 patients were lifeless without reliable signs of death. In 642 of these patients (3.8%) resuscitation was initiated (median age 68 years). The remaining 633 patients (3.7%) were declared dead at the scene without any resuscitation attempt (median age 77 years). These latter patients would have been attempted resuscitated, had the anaesthesiologist not been present. In 54.5% of cases where documentation was available in the patient records, reasons for not resuscitating these patients included time elapsed from incident to contact with physician, 'overall assessment', chronic disease, or do-not-resuscitate order. CONCLUSION: In one patient in 30, the MECU refrained from futile resuscitation in cases where legislation required an EMT to initiate resuscitation. This practice reduced unethical attempts of resuscitation, reduced unnecessary emergency ambulance transports, and reduced the work load of the hospital resuscitation teams for one unnecessary alarm every third day. Differentiating between lifeless patients and dead patients not exhibiting reliable signs of death, however, is a complex task which is only sparsely documented.

Interventions to reduce cognitive impairments following critical illness: a topical systematic review.

BACKGROUND: Critical illness is associated with cognitive impairments. Effective treatment or prevention has not been established. The aim of this review was to create a systematic summary of the current evidence concerning clinical interventions during intensive care admission to reduce cognitive impairments after discharge. METHODS: Medline, Embase, Cochrane Central, PsycInfo and Cinahl were searched. Inclusion criteria were studies assessing the effect of interventions during intensive care admission on cognitive function in adult patients. Studies were excluded if they were reviews or reported solely on survivors of cardiac arrest, stroke or traumatic brain injury. RESULTS: Of 4877 records were identified. Seven studies fulfilled the eligibility criteria. The interventions described covered strategies for enteral nutrition, fluids, sedation, weaning, mobilization, cognitive activities, statins and sleep quality improvement. Data were synthesized to provide an overview of interventions, quality, follow-up assessments and neuropsychological outcomes. CONCLUSION: None of the interventions had significant positive effects on cognitive impairments following critical illness. Quality was negatively affected by study limitations, imprecision and indirectness in evidence. Clinical research on cognition is feasible, but large, well designed trials with a specific aim at reducing cognitive impairments are needed.

A randomised, controlled, double-blind trial of ultrasound-guided phrenic nerve block to prevent shoulder pain after thoracic surgery.

Moderate to severe ipsilateral shoulder pain is a common complaint following thoracic surgery. In this prospective, parallel-group study at Odense University Hospital, 76 patients (aged > 18 years) scheduled for lobectomy or pneumonectomy were randomised 1:1 using a computer-generated list to receive an ultrasound-guided supraclavicular phrenic nerve block with 10 ml ropivacaine or 10 ml saline (placebo) immediately following surgery. A nerve catheter was subsequently inserted and treatment continued for 3 days. The study drug was pharmaceutically pre-packed in sequentially numbered identical vials assuring that all participants, healthcare providers and data collectors were blinded. The primary outcome was the incidence of unilateral shoulder pain within the first 6 h after surgery. Pain was evaluated using a numeric rating scale. Nine of 38 patients in the ropivacaine group and 26 of 38 patients in the placebo group experienced shoulder pain during the first 6 h after surgery (absolute risk reduction 44% (95% CI 22-67%), relative risk reduction 65% (95% CI 41-80%); p = 0.00009). No major complications, including respiratory compromise or nerve injury, were observed. We conclude that ultrasound-guided supraclavicular phrenic nerve block is an effective technique for reducing the incidence of ipsilateral shoulder pain after thoracic surgery.

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis.

Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.

Point prevalence of surgical checklist use in Europe: relationship with hospital mortality.

BACKGROUND: The prevalence of use of the World Health Organization surgical checklist is unknown. The clinical effectiveness of this intervention in improving postoperative outcomes is debated. METHODS: We undertook a retrospective analysis of data describing surgical checklist use from a 7 day cohort study of surgical outcomes in 28 European nations (European Surgical Outcomes Study, EuSOS). The analysis included hospitals recruiting >10 patients and excluding outlier hospitals above the 95th centile for mortality. Multivariate logistic regression and three-level hierarchical generalized mixed models were constructed to explore the relationship between surgical checklist use and hospital mortality. Findings are presented as crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 45 591 patients from 426 hospitals were included in the analysis. A surgical checklist was used in 67.5% patients, with marked variation across countries (0-99.6% of patients). Surgical checklist exposure was associated with lower crude hospital mortality (OR 0.84, CI 0.75-0.94; P=0.002). This effect remained after adjustment for baseline risk factors in a multivariate model (adjusted OR 0.81, CI 0.70-0.94; P<0.005) and strengthened after adjusting for variations within countries and hospitals in a three-level generalized mixed model (adjusted OR 0.71, CI 0.58-0.85; P<0.001). CONCLUSIONS: The use of surgical checklists varies across European nations. Reported use of a checklist was associated with lower mortality. This observation may represent a protective effect of the surgical checklist itself, or alternatively, may be an indirect indicator of the quality of perioperative care. CLINICAL TRIAL REGISTRATION: The European Surgical Outcomes Study is registered with ClinicalTrials.gov, number NCT01203605.

Bedside diagnosis of mitochondrial dysfunction after malignant middle cerebral artery infarction.

BACKGROUND: The study explores whether the cerebral biochemical pattern in patients treated with hemicraniectomy after large middle cerebral artery infarcts reflects ongoing ischemia or non-ischemic mitochondrial dysfunction. METHODS: The study includes 44 patients treated with decompressive hemicraniectomy (DCH) due to malignant middle cerebral artery infarctions. Chemical variables related to energy metabolism obtained by microdialysis were analyzed in the infarcted tissue and in the contralateral hemisphere from the time of DCH until 96 h after DCH. RESULTS: Reperfusion of the infarcted tissue was documented in a previous report. Cerebral lactate/pyruvate ratio (L/P) and lactate were significantly elevated in the infarcted tissue compared to the non-infarcted hemisphere (p < 0.05). From 12 to 96 h after DCH the pyruvate level was significantly higher in the infarcted tissue than in the non-infarcted hemisphere (p < 0.05). CONCLUSION: After a prolonged period of ischemia and subsequent reperfusion, cerebral tissue shows signs of protracted mitochondrial dysfunction, characterized by a marked increase in cerebral lactate level with a normal or increased cerebral pyruvate level resulting in an increased LP-ratio. This biochemical pattern contrasts to cerebral ischemia, which is characterized by a marked decrease in cerebral pyruvate. The study supports the hypothesis that it is possible to diagnose cerebral mitochondrial dysfunction and to separate it from cerebral ischemia by microdialysis and bed-side biochemical analysis.

Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets.

BACKGROUND: Mitochondrial dysfunction is an important factor contributing to tissue damage in both severe traumatic brain injury and ischemic stroke. This experimental study explores the possibility to diagnose the condition bedside by utilising intracerebral microdialysis and analysis of chemical variables related to energy metabolism. METHODS: Mitochondrial dysfunction was induced in piglets and evaluated by monitoring brain tissue oxygen tension (PbtO2 ) and cerebral levels of glucose, lactate, pyruvate, glutamate, and glycerol bilaterally. The biochemical variables were obtained by microdialysis and immediate enzymatic analysis. Mitochondrial function was blocked by unilateral infusion of NaCN/KCN (0.5 mol/L) through the microdialysis catheter (N = 5). As a reference, NaCl (0.5 mol/L) was infused by intracerebral microdialysis in one group of animals (N = 3). RESULTS: PbtO2 increased during cyanide infusion and returned to baseline afterwards. The lactate/pyruvate (LP) ratio increased significantly following cyanide infusion because of a marked increase in lactate level while pyruvate remained within normal limits. Glutamate and glycerol increased after cyanide infusion indicating insufficient energy metabolism and degradation of cellular membranes, respectively. CONCLUSION: Mitochondrial dysfunction is characterised by an increased LP ratio signifying a shift in cytoplasmatic redox state at normal or elevated PbtO2 . The condition is biochemically characterised by a marked increase in cerebral lactate with a normal or elevated pyruvate level. The metabolic pattern is different from cerebral ischemia, which is characterised by simultaneous decreases in intracerebral pyruvate and PbtO2 . The study supports the hypothesis that cerebral ischemia and mitochondrial dysfunction may be identified and separated at the bedside by utilising intracerebral microdialysis.

Haemodynamic optimisation in lower limb arterial surgery: room for improvement?

BACKGROUND: Goal-directed therapy has been proposed to improve outcome in high-risk surgery patients. The aim of this study was to investigate whether individualised goal-directed therapy targeting stroke volume and oxygen delivery could reduce the number of patients with post-operative complications and shorten hospital length of stay after open elective lower limb arterial surgery. METHODS: Forty patients scheduled for open elective lower limb arterial surgery were prospectively randomised. The LiDCO™plus system was used for haemodynamic monitoring. In the intervention group, stroke volume index was optimised by administering 250 ml aliquots of colloid intraoperatively and during the first 6 h post-operatively. Following surgery, fluid optimisation was supplemented with dobutamine, if necessary, targeting an oxygen delivery index level ≥ 600 ml/min(/) m(2) in the intervention group. Central haemodynamic data were blinded in control patients. Patients were followed up after 30 days. RESULTS: In the intervention group, stroke volume index, and cardiac index were higher throughout the treatment period (45 ± 10 vs. 41 ± 10 ml/m(2), P < 0.001, and 3.19 ± 0.73 vs. 2.77 ± 0.76 l/min(/) m(2), P < 0.001, respectively) as well as post-operative oxygen delivery index (527 ± 120 vs. 431 ± 130 ml/min(/) m(2), P < 0.001). In the same group, 5/20 patients had one or more complications vs. 11/20 in the control group (P = 0.05). After adjusting for pre-operative and intraoperative differences, the odds ratio for ≥ 1 complications was 0.18 (0.04-0.85) in the intervention group (P = 0.03). The median length of hospital stay did not differ between groups. CONCLUSION: Perioperative individualised goal-directed therapy may reduce post-operative complications in open elective lower limb arterial surgery.

Optimising stroke volume and oxygen delivery in abdominal aortic surgery: a randomised controlled trial.

BACKGROUND: Post-operative complications after open elective abdominal aortic surgery are common, and individualised goal-directed therapy may improve outcome in high-risk surgery. We hypothesised that individualised goal-directed therapy, targeting stroke volume and oxygen delivery, can reduce complications and minimise length of stay in intensive care unit and hospital following open elective abdominal aortic surgery. METHODS: Seventy patients scheduled for open elective abdominal aortic surgery were randomised to individualised goal-directed therapy or conventional therapy. In the intervention group, stroke volume was optimised by 250 ml colloid boluses intraoperatively and for the first 6 h post-operatively. The optimisation aimed at an oxygen delivery of 600 ml/min/m(2) in the post-operative period. Haemodynamic data were collected at pre-defined time points, including baseline, intraoperatively and post-operatively. Patients were followed up for 30 days. RESULTS: Stroke volume index and oxygen delivery index were both higher in the post-operative period in the intervention group. In this group, 27 of 32 achieved the post-operative oxygen delivery index target vs. 18 of 32 in the control group (P = 0.01). However, the number of complications per patient or length of stay in the intensive care unit or hospital did not differ between the groups. CONCLUSION: Perioperative individualised goal-directed therapy targeting stroke volume and oxygen delivery did not affect post-operative complications, intensive care unit or hospital length of stay in open elective abdominal aortic surgery.

Cerebral energy metabolism during induced mitochondrial dysfunction.

BACKGROUND: In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets. METHODS: Ten piglets were included, seven in the experimental group (anesthetized with sevoflurane) and three in the control group (anesthetized with midazolam). PbtO(2) and cerebral levels of glucose, lactate, and pyruvate were monitored bilaterally. The biochemical variables were obtained by intracerebral microdialysis. RESULTS: All global variables were within normal range and did not differ significantly between the groups except for blood lactate that was slightly higher in the experimental group. Mitochondrial dysfunction was observed in the group of animals initially anesthetized with sevoflurane. Cerebral glucose was significantly lower in the experimental group than in the control group whereas lactate and lactate/pyruvate ratio were significantly higher. Pyruvate and tissue oxygen tension remained within normal range in both groups. Changes of intracerebral variables indicating mitochondrial dysfunction were present already from the very start of the monitoring period. CONCLUSION: Intracerebral microdialysis revealed mitochondrial dysfunction by marked increases in cerebral lactate and lactate/pyruvate ratio simultaneously with normal levels of pyruvate and a normal PbtO(2). This metabolic pattern is distinctively different from cerebral ischemia, which is characterized by simultaneous decreases in PbtO(2) and intracerebral pyruvate.

Recirculation usually precedes malignant edema in middle cerebral artery infarcts.

OBJECTIVES: In patients with large middle cerebral artery (MCA) infarcts, maximum brain swelling leading to cerebral herniation and death usually occurs 2-5 days after onset of stroke. The study aimed at exploring the pattern of compounds related to cerebral energy metabolism in infarcted brain tissue. METHODS: Forty-four patients with malignant MCA infarcts were included after decision to perform decompressive hemicraniectomy (DHC). Cerebral energy metabolism was in all patients monitored bedside by 1-3 microdialysis catheters inserted into the infarcted hemisphere during DHC. In 29 of the patients, one microdialysis catheter was also placed in the non-infarcted hemisphere. MCA blood-flow velocity was monitored bilaterally by transcranial Doppler ultrasound. RESULTS: The interstitial glucose levels were in both sides within normal limits throughout the monitoring period. Mean lactate/pyruvate (LP) ratio was very high in infarcted tissue immediately after DHC. The ratio slowly decreased but did not reach normal level during the study period. In the infarcted hemisphere, MCA blood-flow velocities increased from approximately 42 cm/s 1 day prior to DHC (nine of nine patients) to approximately 60 cm/s at day 4. CONCLUSIONS: Normal interstitial glucose level in the infarcted hemisphere in combination with substantial MCA blood-flow velocities bilaterally even before DHC was performed indicates that malignant brain swelling usually commences when the embolus/thrombosis has been largely resolved and recirculation of the infarcted area has started. The protracted increase of the LP ratio in infarcted tissue might indicate mitochondrial dysfunction.

The outcome of critical illness in decompensated alcoholic liver cirrhosis.

BACKGROUND: The mortality of patients suffering from acute decompensated liver disease treated in the intensive care unit (ICU) varies between 50% and 100%. Previously published data suggest that liver-specific score systems are less accurate compared with the ICU-specific scoring systems acute physiology and chronic health evaluation II (APACHE II) and simplified organ failure assessment (SOFA) in predicting outcome. We hypothesized that in a Scandinavian cohort of ICU patients, APACHE II, SOFA, and simplified acute physiology score (SAPS II) were superior to predict outcome compared with the Child-Pugh score. METHODS: A single-centre retrospective cohort analysis was conducted in a university-affiliated ICU. Eighty-seven adult patients with decompensated liver alcoholic cirrhosis were admitted from January 2007 to January 2010. RESULTS: The patients were severely ill with median scores: SAPS II 60, SOFA (day 1) 11, APACHE II 31, and Child-Pugh 12. Receiver operating characteristic curves area under curve was 0.79 for APACHE II, 0.83 for SAPS II, and 0.79 for SOFA (day 1) compared with 0.59 for Child-Pugh. In patients only in need of mechanical ventilation, the 90-day mortality was 76%. If respiratory failure was further complicated by shock treated with vasopressor agents, the 90-day mortality increased to 89%. Ninety-day mortality for patients in need of mechanical ventilation, vasoactive medication, and renal replacement therapy because of acute kidney injury was 93%. CONCLUSION: APACHE II, SAPS II, and SOFA were better at predicting mortality than the Child-Pugh score. With three or more organ failures, the ICU mortality was > 90%. APACHE II > 30, SAPS II > 60, and SOFA at day 1 > 12 were all associated with a mortality of > 90%. Referral criteria of patients suffering from decompensated alcoholic liver disease should be revised.

Time to wake up the patients in the ICU: a crazy idea or common sense?

With the first generation of ventilators, it was often necessary to sedate patients to avoid dyssynchrony between patient and ventilator. The standard treatment of patients in need of mechanical ventilation has therefore traditionally included sedation. Modern ventilators are able to simulate the patients breathing efforts to a higher degree, and therefore, deep sedation is no longer necessary. In the last decade, support has grown for a reduction in the use of sedation. The focus has been placed on the correlation between the depth of sedation and the length of mechanical ventilation. It has been shown that a daily wake up trial reduced the time that patients were dependent on mechanical ventilation. Additionally, it has been shown that combining both a spontaneous breathing trial and a daily wake up trial reduced the mechanical ventilation time compared to a spontaneous breathing trial alone. We have recently shown in a randomized study that the use of no sedation, compared to the standard treatment with sedation and a daily wake up trial, reduced the time that patients required mechanical ventilation, the length of the patients' stay in the intensive care unit, and the total length of the hospital stay. All evidence indicates that the use of sedative drugs should be reduced, patients should be mobilized, and each patient's needs should be evaluated on a daily basis to optimize the care of each individual patient.

Inflammatory response in patients undergoing uterine artery embolization as compared to patients undergoing conventional hysterectomy.

BACKGROUND: Uterine fibroids are benign tumors seen in 20-40% of women of childbearing age, and these fibroids are usually treated by hysterectomy. During the last decade, embolization of the uterine arteries with polyvinyl alcohol microparticles has become an alternative treatment. PURPOSE: To investigate whether uterine artery embolization generates a reduced inflammatory response as compared with conventional hysterectomy. MATERIAL AND METHODS: 40 women, 20 in each group, entered this prospective, non-randomized study. The two groups were comparable concerning age, comorbidity, and body-mass index (BMI). RESULTS: We found a significant difference between the inflammatory responses in women undergoing embolization compared with the inflammatory response in women having an abdominal hysterectomy. Women undergoing embolization were subjected to a much smaller inflammatory burden, their total morphine consumption was lower, and their return to work was faster than women subjected to conventional hysterectomy. CONCLUSION: Uterine artery embolization generates a reduced inflammatory response compared with conventional hysterectomy.