Preoperative high-dose glucocorticoids for early recovery after liver resection: randomized double-blinded trial.

BACKGROUND: Glucocorticoids modulate the surgical stress response. Previous studies showed that high-dose preoperative glucocorticoids reduce levels of postoperative inflammatory markers and specific biomarkers of liver damage compared with placebo, and suggested a reduced complication rate and shorter hospital stay after liver surgery. However, there are no studies with a clinical primary outcome or of early recovery outcomes. The aim of this study was to investigate whether a single high dose of preoperative glucocorticoid reduces complications in the immediate postoperative phase after liver surgery. METHODS: This was a single-centre, double-blinded, parallel-group RCT investigating preoperative methylprednisolone 10 mg/kg (high dose) versus dexamethasone 8 mg (standard-dose postoperative nausea prophylaxis) in patients scheduled for open liver resection. The primary outcome was number of patients with a complication in the postanaesthesia care unit; secondary outcomes included duration of hospital stay, pain and nausea during admission, and 30-day morbidity. RESULTS: A total of 174 patients (88 in high-dose group, 86 in standard-dose group) were randomized and analysed (mean(s.d.) age 65(12) years, 67.2 per cent men); 31.6 per cent had no serious co-morbidities and 25.3 per cent underwent major liver resection. Complications occurred in the postanaesthesia care unit in 51 patients (58 per cent) in the high-dose group and 58 (67 per cent) in the standard-dose group (risk ratio 0.86, 95 per cent c.i. 0.68 to 1.08; P = 0.213). Median duration of hospital stay was 4 days in both groups (P = 0.160). Thirty-day morbidity and mortality rates were similar in the two groups. CONCLUSION: A high dose of preoperative glucocorticoids did not reduce acute postoperative complications after open liver resection compared with a standard dose. Registration number: NCT03403517 (http://www.clinicaltrials.gov); EudraCT 2017-002652-81 (https://eudract.ema.europa.eu/).

Effect of pre-operative methylprednisolone on orthostatic hypotension during early mobilization after total hip arthroplasty.

BACKGROUND: Orthostatic hypotension (OH) and intolerance (OI) are common after total hip arthroplasty (THA) and may delay early mobilization. The pathology of OH and OI includes a dysregulated post-operative vasopressor response, by a hitherto unknown mechanism. We hypothesized that OI could be related to the inflammatory stress response which is inhibited by steroid administration. Consequently, this study evaluated the effect of a pre-operative high-dose methylprednisolone on OH and OI early after THA. METHODS: Randomized, double-blind, placebo-controlled study in 59 patients undergoing elective unilateral THA with spinal anesthesia and a standardized multimodal analgesic regime. Patients were allocated (1 : 1) to pre-operative intravenous (IV) methylprednisolone (MP) 125 mg or isotonic saline (C). OH, OI and cardiovascular responses to sitting and standing were evaluated using a standardized mobilization protocol pre-operatively, 6, and 24 h after surgery. Systolic and diastolic arterial pressure and heart rate were measured non-invasively (Nexfin® ). The systemic inflammation was monitored by the C-reactive protein (CRP) response. RESULTS: At 6 h post-operatively, 11 (38%) versus 11 (37%) patients had OH in group MP and group C, respectively (RR 1.02 (0.60 to 1.75; P = 1.00)), whereas OI was present in 9 (31%) versus 13 (43%) patients (RR 0.76 (0.42 to 1.36; P = 0.42)), respectively. At 24 h post-operatively, the prevalence of OH and OI did not differ between groups, though CRP levels were significantly reduced in group MP (P < 0.001). CONCLUSION: Pre-operative administration of 125 mg methylprednisolone IV did not reduce OH or OI compared with placebo despite a reduced inflammatory response.

Iron deficiency and preoperative anaemia in patients scheduled for elective hip- and knee arthroplasty - an observational study.

BACKGROUND AND OBJECTIVES: Preoperative anaemia is prevalent in elderly patients scheduled for major orthopaedic surgery and is associated with increased transfusion risk and postoperative morbidity. New guidelines recommend preoperative correction of anaemia and iron deficiency in all patients with a Hb < 13 g/dl. However, iron deficiency and other causes of preoperative anaemia in hip- (THA) and knee (TKA) arthroplasty are only sparsely studied. MATERIALS AND METHODS: Preoperative Hb and iron status were prospectively collected from 882 unselected elective fast-track THA/TKA patients and analysed according to both WHO anaemia criteria (Hb < 12 g/dl females, <13 g/dl males) and Hb < 13 g/dl for both genders. Iron deficiency (ID) and other possible anaemia causes were classified by ferritin, transferrin saturation, P-cobalamin, P-folate, C-reactive protein and creatinine. RESULTS: Ninety-five (10·8%) and 243 (27·6%) of the study population were WHO anaemic or had a Hb < 13 g/dl, respectively. Transfusion was more common in anaemic vs. non-anaemic patients 43 vs. 13%; (P < 0·001), and in patients with Hb < 13 g/dl vs. Hb > 13 g/dl 28 vs. 11% (P < 0·001). 154 (17·5%) of all patients had ID, and ID was the most common cause of anaemia with a prevalence of 41% in WHO anaemic patients and 33% in patients with Hb < 13 g/dl. A further 19 (20%) and 46 (19%) patients, respectively, had evidence of iron sequestration. CONCLUSION: Anaemia is prevalent prior to THA and TKA with iron deficiency as the most common and reversible cause.

A randomized trial of the effect of low dose epinephrine infusion in addition to tranexamic acid on blood loss during total hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is associated with both intraoperative and postoperative blood loss resulting in anaemia and, in some patients, transfusion of red blood cells. Epinephrine enhances coagulation by several mechanisms. We evaluated the effect of intraoperative low dose infusion of epinephrine on intraoperative and early postoperative blood loss. METHODS: After consent, 106 subjects undergoing THA under spinal anaesthesia were randomly assigned to receive an i.v. infusion of either epinephrine 0.05 µg kg(-1) min(-1) or placebo (saline 0.9%) during the entire surgical procedure. Intraoperative tranexamic acid (TXA) was administered to all subjects. The primary outcome was intraoperative blood loss directly measured by drains and weighing swabs. Secondary outcome was total blood loss at 24 h postoperatively calculated using the Gross formula. RESULTS: Of 106 subjects randomized, 6 were excluded, leaving 100 subjects for analyses. Mean duration of surgery was 58 (21) min. Intraoperative blood loss was 343 (95% CI 300-386) ml in the epinephrine group compared with 385 (353-434) ml in the placebo group, P = 0.228. 24 h blood loss was 902 (800-1004) ml in the epinephrine group compared with 1080 (946-1220) ml in the placebo group, P = 0.038. CONCLUSION: In subjects also receiving TXA, intraoperative low dose epinephrine infusion did not reduce intraoperative blood loss in THA but calculated 24 h blood loss was reduced by 180 ml compared with placebo. Further studies on low dose epinephrine in patients at high risk of significant bleeding are warranted. CLINICAL TRIAL REGISTRATION: NCT 01708642.

Preoperative anaemia and newly diagnosed cancer 1 year after elective total hip and knee arthroplasty.

BACKGROUND: Preoperative anaemia is a well-established risk factor for use of blood transfusions and postoperative morbidity. Consequently, focus on preoperative evaluation of haemoglobin levels is increasing. In this context, iron deficiency anaemia may be a symptom of undiscovered gastrointestinal (GI) cancer requiring further investigation. However, the association between preoperative anaemia and cancer 1 year after elective total hip (THA) and total knee arthroplasty (TKA) is unknown. We evaluated 1-year cancer diagnoses, particularly GI cancers, in anaemic and non-anaemic THA and TKA patients. STUDY DESIGN AND METHODS: A prospective database on preoperative patient characteristics from six Danish orthopaedic centres was cross-referenced with the Danish Cancer Registry for information on diagnoses of new cancers 1 year after surgery. Crude cancer risk estimates were calculated using chi-square and Fisher's exact test in the total study cohort. Adjusted risk estimates were obtained using propensity scores and the Mantel-Haenzel statistic. RESULTS: Of 5400 procedures, 731 (13·5%) were in anaemic patients. These were older and had more comorbidity than non-anaemic patients. There were 17 (2·3%) and 79 (1·6%) new cancers in anaemic and non-anaemic patients, respectively (OR: 1·38; 95% CI: 0·81-2·35, P = 0·228). After propensity matching of 661 anaemic and 1305 non-anaemic patients, we found no association between preoperative anaemia and cancer (OR: 0·94; 95% CI: 0·51-1·73, P = 0·837) or with GI cancers specifically (OR: 0·80; 95% CI: 0·25-2·56, P = 0·707). CONCLUSION: Preoperative anaemia per se may not be related to being diagnosed with cancer 1 year after THA and TKA. The optimal criteria for preoperative referral of anaemic patients to gastroenterologist in elective THA and TKA need further investigation.

Medical care and organisation at the 2012 Roskilde Music Festival: a prospective observational study.

BACKGROUND: Music festivals, with a mix of music, alcohol and camping at the festival site combined with low hygiene, have become an integral part of society and attracts large numbers of guests. Our study was performed in order to increase the very limited knowledge on health-care issues and organisation of major music festivals. METHOD: Pre-defined illness and injury categories were constructed based on categories previously reported from music festivals. We prospectively recorded patient presentations to the Medical Health Care Organisation (MHCO) at the 2012 Roskilde Festival. RESULTS: During 10 days, more than 130,000 guests and volunteers attended the 2012 Roskilde Festival. Ten thousand six hundred thirty patient presentations were registered between the 30th of June and 9th of July 2012 by the MHCO. The majority of patient presentations, 6919, could be handled by first-aid volunteers with different levels of training. The remaining 3473 patient presentations were assessed to require further health-care competencies or additional resources such as prescriptions, medication or suturing. Two hundred thirty-eight patient presentations were triaged to a designated observation area. Two hundred sixty patients were referred to a local hospital, a general practitioner or a dentist. The overall patient presentation rate was 72/1000 attendees, and the transport-to-hospital rate was 1.8/1000 attendees. CONCLUSION: Our study demonstrates that illnesses and injuries are frequent, although mostly minor, in this normally low-risk population consisting of primarily young and healthy guests. However, comparison with other recent events was difficult as only limited data have been published from other music festivals. Future festivals should publish similar data.

Transfusion-related mortality after primary hip arthroplasty--an analysis of mechanisms and confounders.

BACKGROUND AND OBJECTIVES: Bleeding and postoperative anaemia after total hip arthroplasty (THA) may trigger transfusion of red blood cells (RBC). However, large observational studies have reported associations between RBC transfusion and increased postoperative morbidity and mortality. As major bleeding or severe postoperative anaemia is intrinsically linked with RBC transfusion, direct causality between transfusion and adverse outcomes remains unclear. This study aimed to identify possible relations between RBC transfusion, severe bleeding or anaemia and mortality in all patients who died <90 days after THA in Denmark in 2008. MATERIALS AND METHODS: Nationwide review of patient records. Cases of adverse transfusion events, infections following transfusion, severe perioperative bleeding or anaemia and possible causal relations to mortality were identified by two independent reviewers. RESULTS: Of 6932 THA patients, 45 (0·6%) were transfused within 30 days and died <90 days from surgery. Three patients (7%) died from causes possibly related to either severe anaemia, major bleeding alone or major bleeding with transfusion-related acute lung injury, while five (11%) died from infections occurring after RBC transfusion. Mortality in the remaining 37 patients (82%) was of unknown cause (nine patients) or related to patient or surgical factors (28 patients). CONCLUSION: Transfusion-related mortality after THA included cases of major perioperative bleeding or severe postoperative anaemia with delayed RBC transfusion in addition to possible complications to RBC transfusion per se. Future studies should account for pretransfusion haemoglobin and perioperative blood loss when evaluating RBC transfusion-associated outcomes after surgery.

Orthostatic intolerance during early mobilization after fast-track hip arthroplasty.

BACKGROUND: Early postoperative mobilization is a cornerstone in fast-track total hip arthroplasty (THA), but postoperative orthostatic intolerance (OI) may delay early recovery or lead to fainting, falls, and prosthesis dislocation or fracture. However, the prevalence and pathophysiology of OI has not been established after THA. This study evaluated the cardiovascular response and tissue oxygenation to mobilization before and after surgery in relation to OI in fast-track THA patients. METHODS: OI and the cardiovascular response to standing were evaluated with a standardized mobilization protocol, before, 6, and 24 h after surgery in 26 patients undergoing THA with spinal anaesthesia and an opioid-sparing analgesic regime. Haemoglobin, fluid balance, and opioid use were recorded. Systolic (SAP) and diastolic (DAP) arterial pressure, heart rate (HR), stroke volume (SV), cardiac output (CO), and systemic vascular resistance were measured non-invasively (Nexfin(®)) and cerebral ( ) and muscle tissue oxygenation by non-infrared spectroscopy. RESULTS: No patients demonstrated OI before surgery, whereas 11 (42%) and five (19%) patients experienced OI 6 and 24 h after surgery, respectively. OI was associated with decreased orthostatic responses in SAP, DAP, SV, CO, and compared with orthostatic tolerant patients (P<0.05). There was no difference in postoperative haemoglobin concentrations or opioid use between orthostatic intolerant and tolerant patients. CONCLUSIONS: Early postoperative OI is common in patients undergoing THA and is associated with an impaired cardiovascular orthostatic response and decreased cerebral oxygenation.

Transfusion practice in hip arthroplasty--a nationwide study.

BACKGROUND AND OBJECTIVES: The optimal transfusion strategy in hip arthroplasty remains controversial despite existing guidelines. The aim of this study was to evaluate the transfusion practice in patients undergoing primary total hip arthroplasty (THA) or revision total hip arthroplasty (RTHA) in Denmark. MATERIALS AND METHODS: We performed a retrospective cohort study of all patients undergoing THA or RTHA in Denmark in 2008. Primary outcomes were intercentre variation in red blood cell (RBC) transfusion rates and the timing of transfusion related to surgery. RESULTS: Six thousand nine hundred thirty-two THA patients and 1132 RTHA patients were included for analysis of which 1674 (24%) THA and 689 (61%) RTHA patients received RBC transfusion. Of these, 47% of THA and 73% of RTHA patients received transfusion on the day of surgery. Transfusion rates between centres varied from 7 to 71% and between 26 and 85% in THA and RTHA patients, respectively. Patients receiving RBC transfusion had longer length of stay and for THA patients an increased odds-ratio (5·5) of death within 90 days. CONCLUSION: Despite established guidelines, RBC transfusion practice in hip arthroplasty remains highly variable between Danish hospitals. The effect of RBC transfusion on outcome after hip arthroplasty should be established in prospective randomized controlled trials.

Goal-directed fluid therapy: stroke volume optimisation and cardiac dimensions in supine healthy humans.

BACKGROUND: Based on maximisation of cardiac stroke volume (SV), peri-operative individualised goal-directed fluid therapy improves patient outcome. It remains, however, unknown how fluid therapy by this strategy relates to filling of the heart during supine rest as reference for the anaesthetised patient and whether the heart becomes distended. To answer these questions, this study related SV to the diastolic filling of the heart while varying central blood volume (CBV) between hypo- and hyper-volaemia, simulating bleeding, and fluid loading, respectively, when exposing healthy human subjects to head-up (HUT) and head-down tilt (HDT). METHODS: Twelve healthy volunteers underwent graded tilt from 20 degrees HDT to 30 degrees HUT. The end-diastolic dimensions of the heart were assessed by transthoracic echocardiography with independent evaluation of SV by Modelflow. The CBV was monitored by thoracic electrical admittance, central venous oxygenation and pressure, and arterial plasma atrial natriuretic peptide. Also, muscle and brain oxygenation were assessed by near infrared spectroscopy (n=7). RESULTS: The HUT reduced the mentioned indices of CBV, the end-diastolic dimensions of the heart, and SV. Conversely, HDT-enhanced tissue oxygenation and the diastolic filling of the heart, but not SV. CONCLUSIONS: In healthy supine humans, the heart is provided with a volume that is sufficient to secure a maximal SV without distending the heart. The implication for individualised goal-directed fluid therapy is that when a maximal SV is established for patients, cardiac pre-load is comparable to that of supine healthy subjects.

Preload maintenance and the left ventricular response to prolonged exercise in men.

This study examined whether left ventricular function was reduced during 3 h of semi-recumbent ergometer cycling at 70% of maximal oxygen uptake while preload to the heart was maintained via saline infusion. Indices of left ventricular systolic function (end-systolic blood pressure-volume relationship, SBP/ESV) and diastolic filling (ratio of early to late peak filling velocities into the left ventricle, E:A) were calculated during recovery and compared with baseline resting data. During exercise in seven healthy, trained male subjects, an arterial catheter allowed continuous assessment of arterial pressure, stroke volume (SV), cardiac output ( ) and an index of contractility (dP/dt(max)). A venous catheter assessed that central venous pressure (CVP) was maintained throughout rest, exercise and 10 min into recovery. Both systolic blood pressure and heart rate (HR) increased with the onset of exercise (from 132 +/- 5 to 185 +/- 19 mmHg and from 66 +/- 9 to 135 +/- 23 beats min(-1); increases from rest to the end of the first 5 min of exercise in SBP and HR, respectively) but systolic blood pressure did not change from 30 to 180 min of exercise ( approximately 150 mmHg), while heart rate only increased by 8 +/- 9 beats min(-1) (means +/- s.d.; P > 0.05). The attenuated increase in HR compared with other studies suggests that the maintained CVP ( approximately 5 mmHg) helped to prevent cardiovascular drift in this protocol. Stroke volume, and dP/dt(max) were all increased with the onset of exercise (from 85 +/- 8 to 120 +/- 18 ml, from 5.4 +/- 1.3 to 16.5 +/- 3.3 l min(-1) and from 14.4 +/- 4 to 28 +/- 8 mmHg s(-1); values from rest to the end of the first 5 min of exercise for SV, and dP/dt(max), respectively) and were maintained during exercise. There was no difference in the SBP/ESV ratio from pre- to postexercise. Conversely, E:A was reduced from 2.0 +/- 0.4 to 1.6 +/- 0.5 postexercise (P < 0.05), returning to normal values at 24 h postexercise. This change in diastolic filling could not be fully explained (r(2) = 0.39) by an increased heart rate and, with CVP unchanged, it is likely to represent some depression of intrinsic relaxation properties of left ventricular myocytes. Three hours of semi-supine cycling resulted in no evidence of a depression in left ventricular systolic function, while left ventricular diastolic function declined postexercise.