Spinal Anaesthesia as an Adjunct to General Anaesthesia for Laparoscopic Abdominoperineal Rectal Amputation.

Background: Spinal anaesthesia as an adjunct to general anaesthesia may reduce postoperative pain and opioid consumption after laparoscopic abdominoperineal rectal amputation. We designed a randomized double blinded pilot study with two objectives: 1) to explore potential benefits of spinal anaesthesia as an adjunct to general anaesthesia and 2) to provide power and sample size estimations for potential differences between the groups. Primary outcome measures were postoperative pain and oral morphine equivalent (OMEq) consumption. Methods: Patients scheduled for elective laparoscopic abdominoperineal rectal amputation at the University Hospital of North Norway were randomised to spinal (n=5) or a sham spinal procedure (n=5). Numeric rating scale (NRS) and OMEq were monitored postoperatively for 72 h. Results: Age, sex, body mass index, and ASA were not significantly different between the groups. During surgery, patients in the spinal group received less remifentanil (p=0.06). NRS was lower in the spinal group 1 hr after admittance to the post-anaesthesia care unit (PACU) (p=0.06) and on the first postoperative day at 8 AM (p=0.03). OMEq consumption in the PACU was lower in the spinal group (p=0.008), but no differences between the groups were detected after discharge to the ward. Sample size estimations revealed that eight patients in each group would be needed to study potential NRS differences after admission to the PACU and 23 patients in each group to study potential differences in OMEq consumption on day 1. Conclusion: Spinal anaesthesia as an adjunct to general anaesthesia reduces postoperative pain and opioid consumption after laparoscopic abdominoperineal rectal amputation. Data from the current study should be followed up by a sufficiently powered randomized controlled trial. Clinical Trial Registration: Trial registered at https://clinicaltrials.gov (NCT05406765).

Continuous Infusion of Iohexol to Monitor Perioperative Glomerular Filtration Rate.

Continuous monitoring of the glomerular filtration rate (GFR) in the perioperative setting could provide valuable information about acute kidney injury risk for both clinical and research purposes. This pilot study aimed to demonstrate that GFR measurement by a continuous 72 hrs iohexol infusion in patients undergoing colorectal cancer surgery is feasible. Four patients undergoing robot-assisted colorectal cancer surgery were recruited from elective surgery listings. GFR was determined preoperatively by the single-sample iohexol clearance method, and postoperatively at timed intervals by a continuous iohexol infusion for 72 hrs. Plasma concentrations of creatinine and cystatin C were measured concurrently. GFR was calculated as (iohexol infusion rate (mg/min))/(plasma iohexol concentration (mg/mL)). The association of the three different filtration markers and GFR with time were analysed in generalized additive mixed models. The continuous infusion of iohexol was established in all four patients and maintained throughout the study period without interfering with ordinary postoperative care. Postoperative GFR at 2 hours were elevated compared to the preoperative measurements for patients 1, 2, and 3, but not for patient 4. Whereas patients 1, 2, and 3 had u-shaped postoperative mGFR curves, patient 4 demonstrated a linear increase in mGFR with time. We conclude that obtaining continuous measurements of GFR in the postoperative setting is feasible and can detect variations in GFR. The method can be used as a tool to track perioperative changes in renal function.

A combination of infraclavicular and suprascapular nerve blocks for total shoulder arthroplasty: A case series.

BACKGROUND: Shoulder arthroplasty is associated with significant post-operative pain. Interscalene plexus block is the gold standard for pain management in patients undergoing this surgery, however, alternatives are currently being developed. We hypothesized that a combination of anterior suprascapular nerve block and lateral sagittal infraclavicular block would provide effective post-operative analgesia. Primary aims for this study were to document numeric rating scale (NRS) pain score and use of oral morphine equivalents (OMEq) during the first 24 hours after surgery. Secondary aim was to determine the incidence of hemidiaphragmatic paralysis. METHODS: Twenty patients (ASA physical status I-III) scheduled for shoulder arthroplasty were studied. Four mL ropivacaine 0.5% was administered for the suprascapular nerve block and 15 mL ropivacaine 0.75% for the infraclavicular block. Surgery was performed under general anaesthesia. Paracetamol and prolonged-release oxycodone were prescribed as post-operative analgesics. Morphine and oxycodone were prescribed as rescue pain medication. Diaphragm status was assessed by ultrasound. RESULTS: Median NRS (0-10) at 1, 3, 6, 8 and 24 hours post-operatively were 1, 0, 0, 0 and 3, respectively. NRS at rest during the first 24 post-operative hours was 4 (2.5-4.5 [0-5]), median (IQR [range]). Maximum NRS was 6.5 (5-8 [0-10]) median (IQR [range]). Total OMEq during the first 24 post-operative hours was 52.5 mg (30-60 [26.4-121.5]) median (IQR [range]). Hemidiaphragmatic paralysis was diagnosed in one patient (5%). CONCLUSIONS: The combination of suprascapular and infraclavicular nerve block shows an encouraging post-operative analgesic profile and a low risk for hemidiaphragmatic paralysis after total shoulder arthroplasty.

Opioid consumption in two surgical hospital wards. / Forbruk av opioider ved to kirurgiske sykehusavdelinger.

BACKGROUND: The purpose of the study was to document the consumption of opioids in two surgical departments at the University Hospital of North Norway, Tromsø, in the period 2010-17. MATERIAL AND METHOD: The consumption of opioids in the department of gastrointestinal surgery and the department of cardiovascular and thoracic surgery was obtained from Nord hospital pharmacy. All opioids were converted to oral morphine equivalents. RESULTS: The consumption of morphine in the department of gastrointestinal surgery was reduced from 223 835 oral morphine equivalents per year in the period 2010-13, to 147 641 in the period 2014-17. In the department of cardiovascular and thoracic surgery, the yearly consumption of morphine was reduced from 28 652 oral morphine equivalents in the period 2010-13, to 22 945 in the period 2014-17. The consumption of oxycodone in the department of gastrointestinal surgery increased from 210 643 oral morphine equivalents per year in the period 2010-13, to 376 322 in the period 2014-17. In the department of cardiovascular and thoracic surgery, the consumption of oxycodone increased from 28 922 oral morphine equivalents per year in the period 2010-13, to 123 875 in the period 2014-17. In the department of gastrointestinal surgery, the increase was most evident for oxycodone administered intravenously or subcutaneously. In the department of cardiovascular and thoracic surgery, the largest increase was for oxycodone administered orally. INTERPRETATION: The consumption of opioids increased in both departments studied, and oxycodone constituted the largest part of the increase.

Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients.

BACKGROUND: In critically ill, mechanically ventilated patients, daily interruption of sedation has been shown to reduce the time on ventilation and the length of stay in the intensive care unit (ICU). Data on whether a plan of no sedation, as compared with a plan of light sedation, has an effect on mortality are lacking. METHODS: In a multicenter, randomized, controlled trial, we assigned, in a 1:1 ratio, mechanically ventilated ICU patients to a plan of no sedation (nonsedation group) or to a plan of light sedation (i.e., to a level at which the patient was arousable, defined as a score of -2 to -3 on the Richmond Agitation and Sedation Scale [RASS], on which scores range from -5 [unresponsive] to +4 [combative]) (sedation group) with daily interruption. The primary outcome was mortality at 90 days. Secondary outcomes were the number of major thromboembolic events, the number of days free from coma or delirium, acute kidney injury according to severity, the number of ICU-free days, and the number of ventilator-free days. Between-group differences were calculated as the value in the nonsedation group minus the value in the sedation group. RESULTS: A total of 710 patients underwent randomization, and 700 were included in the modified intention-to-treat analysis. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the nonsedation group than in the sedation group, indicating a greater chance of in-hospital death. The mean RASS score in the nonsedation group increased from -1.3 on day 1 to -0.8 on day 7 and, in the sedation group, from -2.3 on day 1 to -1.8 on day 7. Mortality at 90 days was 42.4% in the nonsedation group and 37.0% in the sedated group (difference, 5.4 percentage points; 95% confidence interval [CI], -2.2 to 12.2; P = 0.65). The number of ICU-free days and of ventilator-free days did not differ significantly between the trial groups. The patients in the nonsedation group had a median of 27 days free from coma or delirium, and those in the sedation group had a median of 26 days free from coma or delirium. A major thromboembolic event occurred in 1 patient (0.3%) in the nonsedation group and in 10 patients (2.8%) in the sedation group (difference, -2.5 percentage points; 95% CI, -4.8 to -0.7 [unadjusted for multiple comparisons]). CONCLUSIONS: Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption. (Funded by the Danish Medical Research Council and others; NONSEDA ClinicalTrials.gov number, NCT01967680.).

Nutritional support for critically ill patients in the intensive care unit. / Ernæring hos kritisk syke intensivpasienter.

Patients in intensive care have increased nutritional needs but are often incapable of eating independently. When should intravenous parenteral nutrition be started, and what is the optimal dose? Here we review the recently updated European guidelines on nutritional support in intensive care patients.

Brachial plexus block of the posterior and the lateral cord using ropivacaine 7.5 mg/mL.

BACKGROUND: We recently showed that the novel combination of a superficial cervical plexus block, a suprascapular nerve block, and the lateral sagittal infraclavicular brachial plexus block (LSIB) provides an alternative anaesthetic method for arthroscopic shoulder surgery. In this study, we hypothesised that the LSIB dose for this shoulder block could be significantly reduced by injecting only towards the shoulder relevant posterior and lateral cords. Our aim was to determine the minimum effective volume in 50% of the patients (MEV50 ) and to estimate the MEV95, when using ropivacaine 7.5 mg/mL to block these cords. METHODS: Twenty-three adult patients scheduled for hand surgery participated in the study. Considering the artery as a clock face with 12 o'clock ventral, the designated volume was injected immediately outside the arterial wall and between 8 and 9 o´clock. The in-plane technique was used. Block success was assessed 30 minutes after withdrawal of the needle. Successful posterior cord block was defined as anaesthesia or analgesia of the axillary nerve. Successful lateral cord block was defined as either anaesthesia or analgesia, or >50% motor block of the musculocutaneous nerve. MEV50 was determined by the staircase up-and-down method. Logistic regression and probit transformation were applied to estimate MEV95 . RESULTS: MEV50 and MEV95 were 7.8 mL [95% confidence interval (CI), 7.3-8.4] and 9.0 mL (95% CI, 7.8-10.3), respectively. CONCLUSION: For single-deposit infraclavicular posterior and lateral cord block, the MEV95 of ropivacaine 7.5 mg/mL was estimated to 9.0 mL.

Glycine and hyperammonemia: potential target for the treatment of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric disorder caused by hepatic dysfunction. Numerous studies dictate that ammonia plays an important role in the pathogenesis of HE, and hyperammonemia can lead to alterations in amino acid homeostasis. Glutamine and glycine are both ammoniagenic amino acids that are increased in liver failure. Modulating the levels of glutamine and glycine has shown to reduce ammonia concentration in hyperammonemia. Ornithine Phenylacetate (OP) has consistently been shown to reduce arterial ammonia levels in liver failure by modulating glutamine levels. In addition to this, OP has also been found to modulate glycine concentration providing an additional ammonia removing effect. Data support that glycine also serves an important role in N-methyl D-aspartate (NMDA) receptor mediated neurotransmission in HE. This potential important role for glycine in the pathogenesis of HE merits further investigations.

Pulmonary vascular clearance of harmful endogenous macromolecules in a porcine model of acute liver failure.

BACKGROUND: Pulmonary complications are common in acute liver failure (ALF). The role of the lungs in the uptake of harmful soluble endogenous macromolecules was evaluated in a porcine model of ALF induced by hepatic devascularization (n = 8) vs. controls (n = 8). In additional experiments, pulmonary uptake was investigated in healthy pigs. Fluorochrome-labeled modified albumin (MA) was applied to investigate the cellular uptake. RESULTS: As compared to controls, the ALF group displayed a 4-fold net increased lung uptake of hyaluronan, and 5-fold net increased uptake of both tissue plasminogen activator and lysosomal enzymes. Anatomical distribution experiments in healthy animals revealed that radiolabeled MA uptake (taken up by the same receptor as hyaluronan) was 53% by the liver, and 24% by the lungs. The lung uptake of LPS was 14% whereas 60% remained in the blood. Both fluorescence and electron microscopy revealed initial uptake of MA by pulmonary endothelial cells (PECs) with later translocation to pulmonary intravascular macrophages (PIMs). Moreover, the presence of PIMs was evident 10 min after injection. Systemic inflammatory markers such as leukopenia and increased serum TNF-α levels were evident after 20 min in the MA and LPS groups. CONCLUSION: Significant lung uptake of harmful soluble macromolecules compensated for the defect liver scavenger function in the ALF-group. Infusion of MA induced increased TNF-α serum levels and leukopenia, similar to the effect of the known inflammatory mediator LPS. These observations suggest a potential mechanism that may contribute to lung damage secondary to liver disease.

A new non-craniotomy model of subarachnoid hemorrhage in the pig: a pilot study.

Subarachnoid hemorrhage (SAH) from rupture of an intracranial arterial aneurysm is a devastating disease affecting young people, with serious lifelong disability or death as a frequent outcome. Large animal models that exhibit all the cardinal clinical features of human SAH are highly warranted. In this pilot study we aimed to develop a non-craniotomy model of SAH in pigs suitable for acute intervention studies. Six Norwegian Landrace pigs received advanced invasive hemodynamic and intracranial pressure (ICP) monitoring. The subarachnoid space, confirmed by a clear cerebrospinal fluid (CSF) tap, was reached by advancing a needle below the ocular bulb through the superior orbital fissure and into the interpeduncular cistern. SAH was induced by injecting 15 mL of autologous arterial blood into the subarachnoid space. Macro- and microanatomical investigations of the pig brain showed a typical blood distribution consistent with human aneurysmal SAH (aSAH) autopsy data. Immediately after SAH induction ICP sharply increased with a concomitant reduction in cerebral perfusion pressure (CPP). ICP returned to near normal values after 30 min, but increased subsequently during the experimental period. Signs of brain edema were confirmed by light microscopy post-mortem. None of the animals died during the experimental period. This new transorbital injection model of SAH in the pig mimics human aSAH and may be suitable for acute intervention studies. However, the model is technically challenging and needs further validation.

Effects of implementing a clinical pharmacist service in a mixed Norwegian ICU.

OBJECTIVES: An unacceptably high proportion of patients admitted to intensive care units (ICUs) develop drug-related problems (DRPs). DRPs might cause harm and increase costs and length of stay. The implementation of a clinical pharmacist service has been shown to detect a high number of DRPs and contributes effectively to solving these across different healthcare systems. However, this has not been prospectively studied in a mixed tertiary Norwegian ICU. METHODS: During a 12-month period from October 2012, a clinical pharmacist was dedicated to review medications 3 h daily (Monday to Friday). DRPs were reported at the ICU conference and included advice by the pharmacist for each case. All DRPs were categorised and the clinical impact was documented for later analysis. Drug-related questions from the staff were categorised and answered. RESULTS: 363 of 549 patients admitted to the ICU received medication reviews. 641 DRPs were detected in 194 of these patients (mean 1.8 DRPs per patient, range 0-25). Too high a dose, significant drug interactions and unnecessary or inappropriate drugs were among the most frequently detected DRPs. 87% of advice given by the pharmacist was accepted or taken into consideration. Typical questions from the nursing staff were related to drug preparation, generic equivalents and drug administration. Questions from doctors were most frequently related to drug dosage, efficiency and adverse effects. CONCLUSIONS: The addition of a dedicated clinical pharmacist to the ICU team improves the quality and safety of medication in a mixed Norwegian ICU.

Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial): study protocol for a randomised controlled trial.

BACKGROUND: Through many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level. No randomised trial has been conducted comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.The objective is to assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients. METHODS/DESIGN: The non-sedation (NONSEDA) trial is an investigator-initiated, randomised, clinical, parallel-group, multinational trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.Inclusion criteria are mechanically ventilated patients with expected duration of mechanical ventilation >24 hours.Exclusion criteria are non-intubated patients, patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2 < 9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.Experimental intervention is non-sedation supplemented with pain management during mechanical ventilation.Control intervention is sedation with a daily wake-up trial.The primary outcome will be all cause mortality at 90 days after randomization. Secondary outcomes will be: days until death throughout the total observation period; coma- and delirium-free days; highest RIFLE score; days until discharge from the intensive care unit (within 28 days); days until the participant is without mechanical ventilation (within 28 days); and proportion of patients with a major cardiovascular outcome. Explorative outcomes will be: all cause mortality at 28 days after randomisation; days until discharge from the intensive care unit; days until the participant is without mechanical ventilation; days until discharge from the hospital; organ failure.Trial size: we will include 700 participants (2 × 350) in order to detect or reject 25% relative risk reduction in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%). DISCUSSION: The trial investigates potential benefits of non-sedation. This might have large impact on the future treatment of mechanically ventilated critically ill patients. TRIAL REGISTER: ClinicalTrials.gov NCT0196768, 09.01.2014.

L-Ornithine phenylacetate reduces ammonia in pigs with acute liver failure through phenylacetylglycine formation: a novel ammonia-lowering pathway.

Glycine is an important ammoniagenic amino acid, which is increased in acute liver failure (ALF). We have previously shown that L-ornithine phenylacetate (OP) attenuates ammonia rise and intracranial pressure in pigs suffering from ALF but failed to demonstrate a stoichiometric relationship between change in plasma ammonia levels and excretion of phenylacetylglutamine in urine. The aim was to investigate the impact of OP treatment on the phenylacetylglycine pathway as an alternative and additional ammonia-lowering pathway. A well-validated and -characterized large porcine model of ALF (portacaval anastomosis, followed by hepatic artery ligation), which recapitulates the cardinal features of human ALF, was used. Twenty-four female pigs were randomized into three groups: (1) sham operated + vehicle, (2) ALF + vehicle, and (3) ALF + OP. There was a significant increase in arterial glycine concentration in ALF (P < 0.001 compared with sham), with a three-fold increase in glycine release into the systemic circulation from the kidney compared with the sham group. This increase was attenuated in both the blood and brain of the OP-treated animals (P < 0.001 and P < 0.05, respectively), and the attenuation was associated with renal removal of glycine through excretion of the conjugation product phenylacetylglycine in urine (ALF + vehicle: 1,060 ± 106 µmol/l; ALF + OP: 27,625 ± 2,670 µmol/l; P < 0.003). Data from this study provide solid evidence for the existence of a novel, additional pathway for ammonia removal in ALF, involving glycine production and removal, which is targeted by OP.

Enhanced recovery after surgery: are we ready, and can we afford not to implement these pathways for patients undergoing radical cystectomy?

Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes.

Guidelines for perioperative care after radical cystectomy for bladder cancer: Enhanced Recovery After Surgery (ERAS(®)) society recommendations.

PURPOSE: Enhanced recovery after surgery (ERAS) pathways have significantly reduced complications and length of hospital stay after colorectal procedures. This multimodal concept could probably be partially applied to major urological surgery. OBJECTIVES: The primary objective was to systematically assess the evidence of ERAS single items and protocols applied to cystectomy patients. The secondary objective was to address a grade of recommendation to each item, based on the evidence and, if lacking, on consensus opinion from our ERAS Society working group. EVIDENCE ACQUISITION: A systematic literature review was performed on ERAS for cystectomy by searching EMBASE and Medline. Relevant articles were selected and quality-assessed by two independent reviewers using the GRADE approach. If no study specific to cystectomy was available for any of the 22 given items, the authors evaluated whether colorectal guidelines could be extrapolated. EVIDENCE SYNTHESIS: Overall, 804 articles were retrieved from electronic databases. Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied. Bowel preparation did not improve outcomes. Early nasogastric tube removal reduced morbidity, bowel recovery time and length of hospital stay. Doppler-guided fluid administration allowed for reduced morbidity. A quicker bowel recovery was observed with a multimodal prevention of ileus, including gum chewing, prevention of PONV and minimally invasive surgery. CONCLUSIONS: ERAS has not yet been widely implemented in urology and evidence for individual interventions is limited or unavailable. The experience in other surgical disciplines encourages the development of an ERAS protocol for cystectomy.

Nitric oxide and L-arginine metabolism in a devascularized porcine model of acute liver failure.

In acute liver failure (ALF), the hyperdynamic circulation is believed to be the result of overproduction of nitric oxide (NO) in the splanchnic circulation. However, it has been suggested that arginine concentrations (the substrate for NO) are believed to be decreased, limiting substrate availability for NO production. To characterize the metabolic fate of arginine in early-phase ALF, we systematically assessed its interorgan transport and metabolism and measured the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) in a porcine model of ALF. Female adult pigs (23-30 kg) were randomized to sham (N = 8) or hepatic devascularization ALF (N = 8) procedure for 6 h. We measured plasma arginine, citrulline, ornithine levels; arginase activity, NO, and ADMA. Whole body metabolic rates and interorgan flux measurements were calculated using stable isotope-labeled amino acids. Plasma arginine decreased >85% of the basal level at t = 6 h (P < 0.001), whereas citrulline and ornithine progressively increased in ALF (P < 0.001 and P < 0.001, vs. sham respectively). No difference was found between the groups in the whole body rate of appearance of arginine or NO. However, ALF showed a significant increase in de novo arginine synthesis (P < 0.05). Interorgan data showed citrulline net intestinal production and renal consumption that was related to net renal production of arginine and ornithine. Both plasma arginase activity and plasma ADMA levels significantly increased in ALF (P < 0.001). In this model of early-phase ALF, arginine deficiency or higher ADMA levels do not limit whole body NO production. Arginine deficiency is caused by arginase-related arginine clearance in which arginine production is stimulated de novo.