Cutaneous sensory block area of the ultrasound-guided subcostal transversus abdominis plane block: an observational study.

BACKGROUND AND OBJECTIVES: The transversus abdominis plane block (TAP) can be applied using different approaches, resulting in varying cutaneous analgesic distributions. This study aimed to assess the cutaneous sensory block area (CSBA) after ultrasound-guided TAP (US-TAP) using the subcostal approach. METHODS: Thirty patients undergoing elective laparoscopic cholecystectomy received a subcostal US-TAP with 20 mL 2.5 mg/mL ropivacaine bilaterally. Measurements were performed 150 min after block application. The CSBA was mapped using cold sensation and a sterile marker, photodocumented, and transferred to a transparency. The area of the CSBA was calculated from the transparencies. RESULTS: The median CSBA of the subcostal US-TAP was 174 cm2 (IQR 119-219 cm2; range 52-398 cm2). In all patients, the CSBA had a periumbilical distribution. In 42 of the 60 (70%) unilateral blocks, the CSBA had both an epigastric and infraumbilical component; in 12 of the 60 (20%) unilateral blocks, it covered only the epigastrium; and in 4 of the 60 (7%) unilateral blocks, it had only an infraumbilical distribution. No CSBA was found in 2 of the 60 (3%) unilateral blocks. In none of the patients did the CSBA cover the abdominal wall lateral to a vertical line through the anterior superior iliac spine. CONCLUSION: The subcostal US-TAP results in a heterogeneous non-dermatomal CSBA with varying size and distribution across the medial abdominal wall.

Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA): A consortium initiative for perioperative research.

Evidence in perioperative care is insufficient. There is an urgent need for large perioperative research programmes, including pragmatic randomised trials, testing daily clinical treatments and unanswered question, thereby providing solid evidence for effects of interventions given to a large and growing number of patients undergoing surgery and anaesthesia. This may be achieved through large collaborations. Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA) is a novel collaborative research network founded to pursue evidence-based answers to major clinical questions in perioperative medicine. The aims of CEPRA are to (1) improve clinical treatment and outcomes and optimise the use of resources for patients undergoing anaesthesia and perioperative care, and (2) disseminate results and inform caretakers, patients and relatives, and policymakers of evidence-based treatments in anaesthesia and perioperative medicine. CEPRA is inclusive in its concept. We aim to extend our collaboration with all relevant clinical collaborators and patient associations and representatives. Although initiated in Denmark, CEPRA seeks to develop an international network infrastructure, for example, with other Nordic countries. The work of CEPRA will follow the highest methodological standards. The organisation aims to structure and optimise any element of the research collaboration to reduce economic costs and harness benefits from well-functioning research infrastructure. This includes successive continuation of trials, harmonisation of outcomes, and alignment of data management systems. This paper presents the initiation and visions of the CEPRA network. CEPRA aims to be inclusive, patient-focused, methodologically sound, and to optimise all aspects of research logistics. This will translate into faster research conduct, reliable results, and accelerated clinical implementation of results, thereby benefiting millions of patients whilst being cost and labour-saving.

Ultrasound-guided peripheral nerve blocks for preoperative pain management in hip fractures: a systematic review.

Systematic reviews associate peripheral nerve blocks based on anatomic landmarks or nerve stimulation with reduced pain and need for systemic analgesia in hip fracture patients. We aimed to investigate the effect of ultrasound-guided nerve blocks compared to conventional analgesia for preoperative pain management in hip fractures. Five databases were searched until June 2021 to identify randomised controlled trials. Two independent authors extracted data and assessed risk of bias. Data was pooled for meta-analysis and quality of evidence was evaluated using Grades of Recommendation Assessment, Development and Evaluation (GRADE). We included 12 trials (976 participants) comparing ultrasound-guided nerve blocks to conventional systemic analgesia. In favour of ultrasound, pain measured closest to two hours after block placement decreased with a mean difference of -2.26 (VAS 0 to 10); (p < 0.001) 95% CI [-2.97 to -1.55]. In favour of ultrasound, preoperative analgesic usage of iv. morphine equivalents in milligram decreased with a mean difference of -5.34 (p=0.003) 95% CI [-8.11 to -2.58]. Time from admission until surgery ranged from six hours to more than three days. Further, ultrasound-guided nerve blocks may be associated with a lower frequency of delirium: risk ratio 0.6 (p = 0.03) 95% CI [0.38 to 0.94], fewer serious adverse events: risk ratio 0.33 (p = 0.006) 95% CI [0.15 to 0.73] and higher patient satisfaction: mean difference 25.9 (VAS 0 to 100) (p < 0.001) 95% CI [19.74 to 32.07]. However, the quality of evidence was judged low or very low. In conclusion, despite low quality of evidence, ultrasound-guided blocks were associated with benefits compared to conventional systemic analgesia.

Optimal peripheral nerve block after minimally invasive colon surgery - a study protocol for a randomised trial.

Introduction Transversus abdominis plane (TAP) blocks are used for post-operative pain management, but their efficacy remains unclear. We aim to investigate the effect of two TAP block methods in minimally invasive colon surgery. Methods This will be a double-blind, randomised and controlled multicentre trial including 360 adults who are planned for elective minimally invasive colon surgery with curative intent for colon neoplasia. The participants are randomised to one of three arms: active ultrasound-guided TAP (US-TAP) and placebo laparoscopic assisted TAP (L-TAP), placebo US-TAP and active L-TAP, or placebo US-TAP and placebo L-TAP. The primary outcome is morphine dose equivalents administered during the first 24 hours after surgery. Secondary outcomes are pain on the first post-operative day, length of stay, post-operative nausea and vomiting, and quality of recovery measured using the Quality of Recovery 15 questionnaire. Statistical analysis will determine any superiority of US-TAP and L-TAP versus placebo, and any non-inferiority of L-TAP compared with US-TAP. The latter will only be tested if superiority to placebo is shown. Primary and secondary outcomes will be analysed as intention-to-treat regarding superiority and as intention-to-treat and per protocol regarding non-inferiority. Conclusion This will be the first ever blinded multicentre trial comparing L-TAP, US-TAP and placebo in daily clinical practice. The study has the potential to determine the role of the TAP in minimally invasive colon surgery. Funding A and JC Tvergaards Fond, Helen Rudes Fond, Fru Olga Bryde Nielsens Fond, Aage og Johanne Louis-Hansen Fond, Medicine and Treatment Research Fund of the Danish Regions and a Research Grant from Copenhagen University Hospital - North Zealand Hospital. Trial registration ClinicalTrials.gov: NCT04311099.

Intraindividual variation of the transversus abdominis plane block: an exploratory study in healthy volunteers.

INTRODUCTION: The transversus abdominis plane block is widely used in postoperative pain management after abdominal surgery. However, large interindividual variation in the cutaneous distribution area of the block has been demonstrated. The purpose of the present study was to explore the reproducibility of the block by determining the intraindividual variation when repeating the block on two separate days. METHODS: Ultrasound-guided posterior transversus abdominis plane blocks were performed in 16 healthy volunteers and repeated after at least 2 days. Cutaneous sensory block areas and distributions, thresholds for mechanical stimulation, abdominal muscle thicknesses at rest and during maximal contraction, waist circumferences and block duration times were measured on both days. Outcome measurements from the 2 days were compared using a one-sample t-test and intraclass correlation coefficients were calculated for each parameter. Agreement was evaluated visually using Bland-Altman plots. RESULTS: None of the mean values of the outcome measurements differed significantly between the 2 days. Intraclass correlation coefficient was 0.75 (moderate-to-good reliability) for lateral abdominal muscle thickness during maximal contraction, but ranges from -0.07 to 0.67 were found for all other outcome measurements (poor-to-moderate reliability). CONCLUSION: We found a moderate-to-good reproducibility for lateral abdominal muscle thickness during maximal voluntary contraction, but a moderate-to-poor reproducibility for all other block characteristics. However, the cutaneous distribution of the block was still located primarily inferior to a horizontal line through the umbilicus and lateral relative to a vertical line through the anterior superior iliac spine.

A randomized controlled trial evaluating the impact of selective axillary nerve block after arthroscopic subacromial decompression.

BACKGROUND: The sensory innervation of the shoulder is complex and there are variations in the branching patterns of the sensory fibres. Articular branches from the axillary nerve to the subacromial bursa are described in more than 50% of investigated shoulders but the isolated contribution of sensory input from the axillary nerve has never been investigated clinically. We hypothesized that a selective block of the axillary nerve would reduce morphine consumption and pain after arthroscopic subacromial decompression. METHODS: We included 60 patients in a randomized, blinded, placebo-controlled study. Patients were randomized to a preoperative selective ultrasound-guided axillary nerve block with 20 mL ropivacaine (7.5 mg/mL) or 20 mL saline. Primary outcome was intravenous morphine consumption 0-4 h postoperatively. Secondary outcome was postoperative pain evaluated by a visual analogue scale (VAS) score (0-100). RESULTS: We analysed data from 50 patients and found no significant difference in 0-4 h postoperative morphine consumption between the two groups (ropivacaine 14 mg, placebo 18 mg (P = 0.12)). There was a reduction in postoperative pain: VAS 0-4 h (area under the curve) (ropivacaine 135, placebo 182 (P = 0.03)), VAS after 8 h (ropivacaine 9, placebo 20 (P = 0.01)) and VAS after 24 h (ropivacaine 7, placebo 18 (P = 0.04)). Eight out of 19 patients with a successful selective axillary nerve block needed an interscalene brachial plexus escape block. CONCLUSIONS: Selective block of the axillary nerve has some pain relieving effect, but in this setting the effect was unpredictable, variable and far from sufficient in a large proportion of the patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01463865). Registered: November 1, 2011.

Longitudinal neural exposure to local anesthetic and nerve block duration: a retrospective analysis of experimental data from healthy volunteer trials.

BACKGROUND AND OBJECTIVES: Characteristics of a nerve block depend on the distribution of local anesthetic (LA) close to the nerve. The relationship between longitudinal distribution of LA and nerve block characteristics has not been investigated in vivo, but one in vitro study showed decrements in action potential amplitudes with increasing exposure length. We describe the influence of longitudinal neural exposure to LA on nerve block duration adjusted for other likely influential factors. METHODS: We analyzed data from an ethical board approved prospective consecutive collected dataset of 180 healthy volunteers with a common peroneal nerve block (2.5-20 mL, 5-40 mg of ropivacaine). Data were retrieved from three independent randomized controlled trials. The longitudinal neural exposure to LA in millimeters was evaluated using ultrasound. Interventional covariates and demographics were retrieved. Nerve block duration, the dependent variable in the primary assessment, was defined as time of insensitivity to a cold stimulus and was evaluated blinded to all other covariates. Using a multiple linear mixed-effects model, we explored the association between neural exposure to LA and nerve block duration. RESULTS: We found a significant positive association between longitudinal neural exposure to LA and block duration (p<0.01). A 10% increase in longitudinal exposure resulted in an 8.7 (2.5; 15) min increase in block duration. LA dose was associated to block duration (p<0.001) but LA volume had no impact (p=0.93). CONCLUSIONS: Longitudinal neural exposure to LA was significantly associated with nerve block duration. LA dose was the strongest determinant for block duration whereas LA volume had no influence.

Ultrasound guided repositioning of a new suture-method catheter for adductor canal block - a randomized pilot study in healthy volunteers.

BACKGROUND: We performed a randomized, blinded pilot study in 12 volunteers to assess the feasibility to reposition an intentionally displaced suture-method catheter for two different insertion techniques for adductor canal block. METHODS: Each volunteer had an ultrasound-guided suture-method catheter placed in the adductor canal (AC) in both legs. The catheters were placed using a perpendicular technique in one leg and a parallel technique in the other leg, according to randomization. 15 mL lidocaine 1% (LA) was injected in each catheter. Successful primary placement was defined as combined LA spread within the AC and loss of cold sensation 15 min after injection. All catheters were intentionally displaced, and subsequently repositioned using ultrasound. Another dose of lidocaine (15 mL 1%) was injected through the catheters and assessed for successful repositioning. RESULTS: Successful primary placement was achieved in 83% (95% CI 55-95%) of catheters placed perpendicular to the AC, and in 75% (95% CI 47-91%) of catheters placed parallel to the AC. Of those with successful primary placement, 100% (95% CI 72-100%) of catheters placed perpendicular to the AC, and 67% (95% CI 35-88%)) placed parallel to the AC could be repositioned. CONCLUSIONS: Placement and secondary repositioning after displacement of a suture-method catheter within the adductor canal is achievable. A perpendicular technique seems more reliable. TRIAL REGISTRATION: NCT03315481 clinicaltrials.gov . The study was submitted on March 1, 2017. Due to clerical error, the study was posted on October 20, 2017.

Routine blood tests are associated with short term mortality and can improve emergency department triage: a cohort study of >12,000 patients.

BACKGROUND: Prioritization of acutely ill patients in the Emergency Department remains a challenge. We aimed to evaluate whether routine blood tests can predict mortality in unselected patients in an emergency department and to compare risk prediction with a formalized triage algorithm. METHODS: A prospective observational cohort study of 12,661 consecutive admissions to the Emergency Department of Nordsjælland University Hospital during two separate periods in 2010 (primary cohort, n = 6279) and 2013 (validation cohort, n = 6383). Patients were triaged in five categories by a formalized triage algorithm. All patients with a full routine biochemical screening (albumin, creatinine, c-reactive protein, haemoglobin, lactate dehydrogenase, leukocyte count, potassium, and sodium) taken at triage were included. Information about vital status was collected from the Danish Central Office of Civil registration. Multiple logistic regressions were used to predict 30-day mortality. Validation was performed by applying the regression models on the 2013 validation cohort. RESULTS: Thirty-day mortality was 5.3%. The routine blood tests had a significantly stronger discriminative value on 30-day mortality compared to the formalized triage (AUC 88.1 [85.7;90.5] vs. 63.4 [59.1;67.5], p < 0.01). Risk stratification by routine blood tests was able to identify a larger number of low risk patients (n = 2100, 30-day mortality 0.1% [95% CI 0.0;0.3%]) compared to formalized triage (n = 1591, 2.8% [95% CI 2.0;3.6%]), p < 0.01. CONCLUSIONS: Routine blood tests were strongly associated with 30-day mortality in acutely ill patients and discriminatory ability was significantly higher than with a formalized triage algorithm. Thus routine blood tests allowed an improved risk stratification of patients presenting in an emergency department.

Transient impairment of the axolemma following regional anaesthesia by lidocaine in humans.

The local anaesthetic lidocaine is known to block voltage-gated Na(+) channels (VGSCs), although at high concentration it was also reported to block other ion channel currents as well as to alter lipid membranes. The aim of this study was to investigate whether the clinical regional anaesthetic action of lidocaine could be accounted for solely by the block of VGSCs or whether other mechanisms are also relevant. We tested the recovery of motor axon conduction and multiple measures of excitability by 'threshold-tracking' after ultrasound-guided distal median nerve regional anaesthesia in 13 healthy volunteers. Lidocaine caused rapid complete motor axon conduction block localized at the wrist. Within 3 h, the force of the abductor pollicis brevis muscle and median motor nerve conduction studies returned to normal. In contrast, the excitability of the motor axons at the wrist remained markedly impaired as indicated by a 7-fold shift of the stimulus-response curves to higher currents with partial recovery by 6 h and full recovery by 24 h. The strength-duration properties were abnormal with markedly increased rheobase and reduced strength-duration time constant. The changes in threshold during electrotonus, especially during depolarization, were markedly reduced. The recovery cycle showed increased refractoriness and reduced superexcitability. The excitability changes were only partly similar to those previously observed after poisoning with the VGSC blocker tetrodotoxin. Assuming an unaltered ion-channel gating, modelling indicated that, apart from up to a 4-fold reduction in the number of functioning VGSCs, lidocaine also caused a decrease of passive membrane resistance and an increase of capacitance. Our data suggest that the lidocaine effects, even at clinical 'sub-blocking' concentrations, could reflect, at least in part, a reversible structural impairment of the axolemma.

Abnormal vital signs are strong predictors for intensive care unit admission and in-hospital mortality in adults triaged in the emergency department - a prospective cohort study.

BACKGROUND: Assessment and treatment of the acutely ill patient have improved by introducing systematic assessment and accelerated protocols for specific patient groups. Triage systems are widely used, but few studies have investigated the ability of the triage systems in predicting outcome in the unselected acute population. The aim of this study was to quantify the association between the main component of the Hillerød Acute Process Triage (HAPT) system and the outcome measures; Admission to Intensive Care Unit (ICU) and in-hospital mortality, and to identify the vital signs, scored and categorized at admission, that are most strongly associated with the outcome measures. METHODS: The HAPT system is a minor modification of the Swedish Adaptive Process Triage (ADAPT) and ranks patients into five level colour-coded triage categories. Each patient is assigned a triage category for the two main descriptors; vital signs, T(vitals), and presenting complaint, T(complaint). The more urgent of the two determines the final triage category, T(final). We retrieved 6279 unique adult patients admitted through the Emergency Department (ED) from the Acute Admission Database. We performed regression analysis to evaluate the association between the covariates and the outcome measures. RESULTS: The covariates, T(vitals), T(complaint) and T(final) were all significantly associated with ICU admission and in-hospital mortality, the odds increasing with the urgency of the triage category. The vital signs best predicting in-hospital mortality were saturation of peripheral oxygen (SpO(2)), respiratory rate (RR), systolic blood pressure (BP) and Glasgow Coma Score (GCS). Not only the type, but also the number of abnormal vital signs, were predictive for adverse outcome. The presenting complaints associated with the highest in-hospital mortality were 'dyspnoea' (11.5%) and 'altered level of consciousness' (10.6%). More than half of the patients had a T(complaint) more urgent than T(vitals), the opposite was true in just 6% of the patients. CONCLUSION: The HAPT system is valid in terms of predicting in-hospital mortality and ICU admission in the adult acute population. Abnormal vital signs are strongly associated with adverse outcome, while including the presenting complaint in the triage model may result in over-triage.

The formation and design of the 'Acute Admission Database'- a database including a prospective, observational cohort of 6279 patients triaged in the emergency department in a larger Danish hospital.

BACKGROUND: Management and care of the acutely ill patient has improved over the last years due to introduction of systematic assessment and accelerated treatment protocols. We have, however, sparse knowledge of the association between patient status at admission to hospital and patient outcome. A likely explanation is the difficulty in retrieving all relevant information from one database. The objective of this article was 1) to describe the formation and design of the 'Acute Admission Database', and 2) to characterize the cohort included. METHODS: All adult patients triaged at the Emergency Department at Hillerød Hospital and admitted either to the observationary unit or to a general ward in-hospital were prospectively included during a period of 22 weeks. The triage system used was a Danish adaptation of the Swedish triage system, ADAPT. Data from 3 different data sources was merged using a unique identifier, the Central Personal Registry number; 1) Data from patient admission; time and date, vital signs, presenting complaint and triage category, 2) Blood sample results taken at admission, including a venous acid-base status, and 3) Outcome measures, e.g. length of stay, admission to Intensive Care Unit, and mortality within 7 and 28 days after admission. RESULTS: In primary triage, patients were categorized as red (4.4%), orange (25.2%), yellow (38.7%) and green (31.7%). Abnormal vital signs were present at admission in 25% of the patients, most often temperature (10.5%), saturation of peripheral oxygen (9.2%), Glasgow Coma Score (6.6%) and respiratory rate (4.8%). A venous acid-base status was obtained in 43% of all patients. The majority (78%) had a pH within the normal range (7.35-7.45), 15% had acidosis (pH < 7.35) and 7% had alkalosis (pH > 7.45). Median length of stay was 2 days (range 1-123). The proportion of patients admitted to Intensive Care Unit was 1.6% (95% CI 1.2-2.0), 1.8% (95% CI 1.5-2.2) died within 7 days, and 4.2% (95% CI 3.7-4.7) died within 28 days after admission. CONCLUSIONS: Despite challenges of data registration, we succeeded in creating a database of adequate size and data quality. Future studies will focus on the association between patient status at admission and patient outcome, e.g. admission to Intensive Care Unit or in-hospital mortality.

[Fatal course of a patient during in vitro fertilisation treatment]. / Fatalt forløb ved in vitro-fertilisation.

Chylomicronaemia syndrome is a rare disorder primarily caused by a genetic defect which increases triglycerides, combined with a secondary inducing factor. We describe the fatal course of a 33-year-old, pregnant woman with known dyslipidaemia who had been treated with in vitro fertilisation and developed chylomicronaemia syndrome with severe hypertriglyceridaemia, hypertriglyceridaemia-induced acute pancreatitis and septic shock. Appropriate treatment including close monitoring, severe restriction of dietary fat intake and early plasmapheresis is emphasized - especially during pregnancy.

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men.

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well-trained males (age 25 +/- 2 years (mean +/- S.E.M.); peak oxygen consumption : 62 +/- 1 ml min(-1) kg(-1) (completed four randomised trials: 120 min bicycling at 55% 4 h after receiving either 7.5 IU (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc. In all studies a standardized meal was given 2 h after GH or Plc injection. GH administration resulted in an approximately 60-fold increase in serum GH concentration at rest (P < 0.0001) and during exercise (P < 0.0001). The increase in serum GH was followed by an increase in circulating glycerol at rest (8%, P < 0.0001). When combined with exercise the increase in plasma glycerol was more pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this increase in fat mobilization did not increase fat oxidation during exercise (indirect calorimetry). In conclusion, GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone, but did not further augment whole body fat oxidation.

Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men.

The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups. The study consisted of two 24-h measurements (indirect calorimetry), separated by 2 wk of either Plc or GH injections (6 IU/day). At baseline, no significant differences were observed between the two groups in any of the measured anthropometric, hormonal, or metabolic parameters, neither did the parameters change over time in the Plc group. GH-adm. resulted in a 4.4% increase in 24-h EE (P < 0.05) and an increase in fat oxidation by 29% (P < 0.05). However, a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast (0.84 +/- 0.1 to 0.79 +/- 0.1, P < 0.05). Furthermore, lean body mass (LBM) was increased by GH-adm. only [62.8 +/- 2.5 kg (baseline) vs. 64.7 +/- 2.4 kg (after), P < 0.001]. In conclusion, GH-adm. increases 24-h EE, which may be partly explained by increased LBM. Furthermore, GH-adm. stimulates fat combustion, especially in the postabsorptive state.

Fat metabolism in exercise--with special reference to training and growth hormone administration.

Despite abundance of fat, exclusive dependency on fat oxidation can only sustain a metabolic rate corresponding to 50-60% of VO(2max) in humans. This puzzling finding has been subject to intense research for many years. Lately, it has gained renewed interest as a consequence of increased obesity and physical inactivity imposed by Western lifestyle. Why are humans so poor at metabolizing fat? Can fat metabolism be manipulated by exercise, training, diet and hormones? And why is fat stored in specialized adipose tissue and not just as lipid droplets inside muscle cells? In the present review, human fat metabolism is discussed in relation to how human fat metabolism is designed. Limitations in this design are explored and examples of different designs for fat metabolism from animal physiology are included to illustrate these limitations. Various means of manipulating fat metabolism are discussed with special emphasis on exercise, training, growth hormone (GH) physiology and GH administration. It is concluded that fat stores, non-esterified fatty acids (NEFAs) availability and enzymes for fat oxidation can be increased substantially. However, it is almost impossible to increase fat oxidation during endurance exercise at higher intensities. It seems that, for some reason, the human being is far from optimally designed for fat oxidation during exercise. Acute GH administration has several unexpected effects on fat and carbohydrate metabolism during aerobic exercise, and future research in this area is likely to provide valuable information with respect to GH physiology and the regulation of fat and carbohydrate metabolism during aerobic exercise.

Acute growth hormone administration causes exaggerated increases in plasma lactate and glycerol during moderate to high intensity bicycling in trained young men.

We studied the acute effects of a single, sc GH dose on exercise performance and metabolism during bicycling. Seven highly trained men [age, 26 +/- 1 yr (mean +/- SEM); weight, 77 +/- 3 kg; maximal oxygen uptake, 65 +/- 1 ml O(2).min(-1).kg(-1)] performed 90 min of bicycling 4 h after receiving 7.5 IU (2.5 mg) GH or placebo in a randomized, double-blinded, cross-over design trial. A standardized pre-exercise meal was given 2 h before exercise. Blood was sampled at rest and during exercise and analyzed for GH, IGF-I, glucose, lactate, insulin, glycerol, and nonesterified fatty acids (NEFA). In the placebo trial, all subjects completed the exercise protocol without any difficulties. In contrast, two subjects were not able to complete the exercise protocol in the GH trial, and one subject barely managed to complete the protocol. In addition, GH administration resulted in exaggerated increases in plasma lactate concentrations during exercise (P < 0.0001). The combined lipolytic effect of GH and exercise, evidenced by increased plasma glycerol and serum NEFA concentrations, was 3-fold greater than the effect of exercise alone (P < 0.0001), but this increased substrate availability did not result in increased whole body fat oxidation (indirect calorimetry). Plasma glucose was, on average, 9% higher during exercise after GH administration compared with placebo (P < 0.0001). We conclude that a single, relevant GH dose causes exaggerated increases in plasma lactate and glycerol as well as serum NEFA during 90 min of subsequent bicycling at moderate to high intensity. The exaggerated increase in plasma lactate may be associated with substantially decreased exercise performance.

Subcutaneous abdominal adipose tissue lipolysis during exercise determined by arteriovenous measurements in older women.

OBJECTIVES: To characterize the lipolytic response in the subcutaneous abdominal adipose tissue in older women to endurance exercise. DESIGN: Cross-sectional exercise study. SETTING: Exercise laboratory, Copenhagen, Denmark. PARTICIPANTS: Seven healthy, older women (mean age +/- standard error = 75 +/- 2 years); weight: 67.8 +/- 4.9 kg; body fat: 40 +/- 3; maximal oxygen uptake (VO2max): 1.43 +/- 0.07 L.min 1). MEASUREMENTS: Body composition (dual energy x-ray absorptiometry (DEXA)), maximal oxygen uptake (VO2max, maximal cycling test), lipolytic response to exercise (arterial and adipose tissue venous catheterization at rest and during 60 minutes of continuous cycling at a load corresponding to 60 of VO2max), adipose tissue blood flow (ATBF) (133Xenon (133Xe) washout), oxygen consumption and respiratory exchange ratio during exercise (indirect calorimetry), whole blood glycerol, plasma nonesterified fatty acids (NEFA), lactate, glucose, epinephrine, norepinephrine, insulin, serum growth hormone, and hematocrit. RESULTS: Glycerol and NEFA mobilization rates increased by 250 and 180, respectively, from rest to exercise. This was achieved primarily by an increase in veno-arterial differences, because ATBF did not increase significantly. NEFA:glycerol mobilization ratio was about two at rest and remained at that level during exercise, indicating significant local reesterification in both conditions. After an initial decrease, arterial plasma NEFA concentration increased significantly, by 26, indicating that NEFA delivery exceeded muscle uptake. CONCLUSIONS: Older women are capable of prompt and substantial increase in subcutaneous abdominal adipose tissue glycerol and NEFA mobilization rates in response to moderate acute endurance exercise. The lipolytic response matches skeletal muscle NEFA uptake, and decreased ability to mobilize fat during exercise is therefore not likely to cause increased fat mass with advancing age.

Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men.

OBJECTIVE: Our objective was to study the effect of recombinant human growth hormone (rhGH) on hepatic cytochrome P450 (CYP) activity in 30 healthy elderly men. METHODS: The study was carried out as a randomized, double-blind, placebo-controlled parallel-group study. rhGH or placebo was administered for a period of 12 weeks. CYP activity was measured before, after 12 weeks of rhGH and placebo administration, and at 4 weeks after termination of rhGH and placebo administration with use of the biomarker reactions of CYP1A2 (caffeine), CYP2C19 (mephenytoin), CYP2D6 (sparteine), CYP3A4 (endogenous cortisol metabolism), and antipyrine clearance as common markers of CYP activity. RESULTS: The metabolic ratio of caffeine increased significantly in the group that received growth hormone compared with placebo (median difference, 4.55; 95% confidence interval (CI), 1.64 to 8.60; versus -0.90; 95% CI, -5.70 to 1.36), indicating an induction of CYP1A2. Moreover, the S/R ratio of mephenytoin showed a small but significant increase (median difference, 0.02; 95% CI, 0 to 0.31; versus 0; 95% CI, -0.01 to 0.06), indicating an inhibition of CYP2C19. There were no significant changes of the metabolic ratios of cortisol and sparteine or the antipyrine clearance compared with placebo. CONCLUSIONS: These results indicate that growth hormone induces CYP1A2 and, to a lesser extent, inhibits CYP2C19 in elderly men, but it exerts no effects on CYP2D6 and CYP3A4. Although the induction of CYP1A2 may be of some clinical relevance, the small inhibition of CYP2C19 is probably unimportant.

GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men.

GH administration, either alone or combined with resistance exercise training (RT), has attracted interest as a means of increasing muscle mass and strength in the elderly. In the present study, 31 healthy, elderly men [age, 74 +/- 1 yr (mean +/- SEM)] were assigned to either RT [3 sessions/wk, 3-5 sets of 8-12 repetition maximum (RM)/session] + placebo (n = 8), RT + GH (n = 8), GH (n = 8), or placebo (n = 7) in a randomized, placebo-controlled, double-blinded (RT + placebo and RT + GH) or single-blinded (GH or placebo) design. Measurements of: 1) isokinetic quadriceps muscle strength; 2) quadriceps muscle power; 3) quadriceps muscle fiber type, size, and myosin heavy chain (MHC) composition; 4) quadriceps cross-sectional area (CSA) [nuclear magnetic resonance imaging (NMRI)]; 5) body composition (dual-energy x-ray absorptiometry scanning); and 6) GH-related serum markers were performed at baseline and after 12 wk. The final GH dose was 1.77 +/- 0.18 IU x d(-1) (approximately 7.2 +/- 0.8 microg x kg(-1) x d(-1)). GH alone had no effect on isokinetic quadriceps muscle strength, power, CSA, or fiber size. However, a substantial increase in MHC 2X isoform was observed with GH administration alone, and this may be regarded as a change into a more youthful MHC composition, possibly induced by the rejuvenating of systemic IGF-I levels. RT + placebo caused substantial increases in quadriceps isokinetic strength, power, and CSA; but these RT induced improvements were not further augmented by additional GH administration. In the RT + GH group, there was a significant decrease in MHC 1 and 2X isoforms, whereas MHC 2A increased. RT, therefore, seems to overrule the changes in MHC composition induced by GH administration alone. Changes in body composition confirmed previous reports of decreased fat mass, increased fat-free mass, and unchanged bone mineral content with GH administration. A high incidence of side effects was reported. Our results do not support a role for GH as a means of increasing muscle strength or mass, either alone or combined with RT, in healthy elderly men; although GH administration alone may induce changes in MHC composition.