Experience with high frequency oscillation ventilation during the 2009 H1N1 influenza pandemic in Australia and New Zealand.

During the 2009 H1N1 pandemic, large numbers of patients had severe respiratory failure. High frequency oscillation ventilation was used as a salvage technique for profound hypoxaemia. Our aim was to compare this experience with high frequency oscillation ventilation during the 2009 H1N1 pandemic with the same period in 2008 by performing a three-month period prevalence study in Australian and New Zealand intensive care units. The main study end-points were clinical demographics, care delivery and survival. Nine intensive care units contributed data. During 2009 there were 22 H1N1 patients (17 adults, five children) and 10 non-H1N1 patients (five adults, five children), while in 2008, 18 patients (two adults, 16 children) received high frequency oscillation ventilation. The principal non-H1N1 high frequency oscillation ventilation indication was bacterial or viral pneumonia (56%). For H1N1 patients, the median duration of high frequency oscillation ventilation was 3.7 days (interquartile range 1.8 to 5) with concomitant therapies including recruitment manoeuvres (22%), prone ventilation (41%), inhaled prostacyclins (18%) and inhaled nitric oxide (36%). Seven patients received extracorporeal membrane oxygenation, six having H1N1. Three patients had extracorporeal membrane oxygenation concurrently, two as salvage therapy following the commencement of high frequency oscillation ventilation. In 2008, no high frequency oscillation ventilation patient received extracorporeal membrane oxygenation. Overall hospital survival was 77% in H1N1 patients, while survival in patients having adjunctive extracorporeal membrane oxygenation was similar to those receiving high frequency oscillation ventilation alone (65% compared to 71%, P = 1.00). Survival rates were comparable to published extracorporeal membrane oxygenation outcomes. High frequency oscillation ventilation was used successfully as a rescue therapy for severe respiratory failure. High frequency oscillation ventilation was only available in a limited number of intensive care units during the H1N1 pandemic.

Granulocyte-colony stimulating factor (G-CSF) as an adjunct to antibiotics in the treatment of pneumonia in adults.

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is a naturally-occurring cytokine that has been shown to increase neutrophil function and number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim or lenograstim) has found extensive use in the treatment of febrile neutropenia, but its role in the treatment of infection in non-neutropenic hosts is less well defined. OBJECTIVES: We explored the role of G-CSF as an adjunct to antibiotics in the treatment of pneumonia in non-neutropenic adults. SEARCH STRATEGY: For this updated review we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2006); MEDLINE (1950 to January 2007); EMBASE (1988 to January 2007); and online databases of clinical trials (www.controlled-trials.com, updated 10 November, 2006). SELECTION CRITERIA: We considered randomized controlled trials (RCTs) which included hospitalized adult patients with either community-acquired pneumonia or hospital-acquired pneumonia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. The primary outcome measure was 28-day mortality. Secondary outcome measures included other markers of mortality as well as markers of adverse events, including organ dysfunction. An assessment of methodological quality was made for each study. MAIN RESULTS: Six studies with a total of 2018 people were identified. G-CSF use appeared to be safe with no increase in the incidence of total serious adverse events (pooled odds ratio (OR) 0.91; 95% confidence interval (CI): 0.73 to 1.14) or organ dysfunction. However, the use of G-CSF was not associated with improved 28-day mortality (pooled OR 0.81; 95% CI: 0.52 to 1.27). AUTHORS' CONCLUSIONS: There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest.

Percutaneus translumbar inferior vena cava venous access in an intensive care patient.

We report the case of a critically ill 30-year-old chronic haemodialysis patient with a history of intravenous substance abuse whose intravenous access sites had become exhausted. She subsequently underwent elective insertion of a percutaneous translumbar inferior vena caval paired Tesio catheter and peripherally inserted central catheter (PICC line). This technique has been used successfully in patients who require longstanding central venous access (hyperalimentation, chemotherapy, chronic renal hemodialysis patients). This approach could be an alternative where the standard access routes have become non-viable.

Granulocyte-Colony Stimulating Factor (G-CSF) as an adjunct to antibiotics in the treatment of pneumonia in adults.

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is a naturally-occurring cytokine that has been shown to increase neutrophil function and number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim or lenograstim) has found extensive use in the treatment of febrile neutropaenia, but its role in the treatment of infection in non-neutropaenic hosts is less well defined. OBJECTIVES: We explored the role of G-CSF as an adjunct to antibiotics in the treatment of pneumonia in non-neutropaenic adults. SEARCH STRATEGY: We searched the following electronic databases in 2003 and updated the search in 2004: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004); MEDLINE (January 1966 to March Week 1, 2004); EMBASE (1998 to December 2003); online databases of clinical trials; and reference lists of articles. We also contacted study authors, manufacturers and distributors of G-CSF. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) which included hospitalised adult patients with either community acquired pneumonia or hospital-acquired pneumonia. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. The primary outcome measure was 28 day mortality. Secondary outcome measures included other markers of mortality as well as markers of adverse events, including organ dysfunction. An assessment of methodological quality was made for each study. MAIN RESULTS: Six studies with a total of 1984 people were identified. G-CSF use appeared to be safe with no increase in the incidence of total serious adverse events (pooled odds ratio (OR) 0.91; 95% confidence interval (CI): 0.73 to 1.14) or organ dysfunction. However, the use of G-CSF was not associated with improved 28 day mortality (pooled OR 0.86; 95% CI: 0.56 to 1.31). REVIEWERS' CONCLUSIONS: There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest.

Terlipressin infusion in catecholamine-resistant shock.

Catecholamine-resistant shock is not uncommon in intensive care. Bolus dose terlipressin (a vasopressin analogue) has been used successfully in this setting allowing cessation of other vasopressor agents. The relative vasopressin deficiency in combination with the restoration of the vascular tone (by blocking adenosine triphosphate potassium-sensitive channels) by exogenous vasopressin may be the explanation of these beneficial effects. We describe a case report where the use of a continuous terlipressin infusion was associated with a dramatic improvement. To our knowledge there have been no previous reports of the use of terlipressin by continuous infusion for the treatment of catecholamine-resistant shock.

Granulocyte colony stimulating factor (G-CSF) as an adjunct to antibiotics in the treatment of pneumonia in adults.

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is a naturally-occurring cytokine that has been shown to increase neutrophil function and number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim or lenograstim) has found extensive use in the treatment of febrile neutropaenia, but its role in the treatment of infection in non-neutropaenic hosts is less well defined. OBJECTIVES: We aimed to explore the role of G-CSF as an adjunct to antibiotics in the treatment of pneumonia in non-neutropaenic adults. SEARCH STRATEGY: A search was performed using the Cochrane Central Register of Controlled Trials (issue 1, 2003); MEDLINE (January 1966 to April 2003); EMBASE (1988 to 2003); online databases of clinical trials; contact with corresponding authors; and contact with the manufacturers and distributors of G-CSF and reviews of citations in publications identified by the above strategies. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) which included hospitalised adult patients with either community acquired pneumonia or hospital-acquired pneumonia. DATA COLLECTION AND ANALYSIS: Studies identified were reviewed independently by two reviewers with data abstracted onto standardized data collection forms. The primary outcome measure was 28 day mortality. Secondary outcome measures included other markers of mortality as well as markers of adverse events, including organ dysfunction. An assessment of methodological quality was made for each study. MAIN RESULTS: G-CSF use appeared to be safe with no increase in the incidence of total serious adverse events (pooled OR 0.91, 95% CI: 0.73, 1.14) or organ dysfunction. However, the use of G-CSF was not associated with improved 28 day mortality (pooled OR 0.99, 95% CI 0.77, 1.29). REVIEWER'S CONCLUSIONS: There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest.

Operation Bali assist--the Royal Darwin Hospital Intensive Care Unit.

On October 12, 2002 the Bali bombing resulted in 62 severely injured patients being evacuated to Royal Darwin Hospital. This paper describes the planning and execution of the Intensive Care Unit disaster plan in the wake of the Bali bombing. There were a total of 20 patients from the Bali blast admitted to the Intensive Care Unit. The disaster operation was successful with all patients admitted, resuscitated, emergency treatment performed and then evacuated to interstate burns units in a timely and efficient manner.

An audit of the use of granulocyte colony-stimulating factor in septic shock.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) stimulates the production of neutrophils and modulates the function and activity of developing and mature neutrophils. In septic shock, the immune system can be considered one of the failing organ systems. G-CSF improves immune function and may be a useful adjunctive therapy in patients with septic shock. AIM: To evaluate the introduction of G-CSF as an adjunct to our standard treatment for community-acquired septic shock. METHODS: We performed a prospective data collection and analysis to determine whether the addition of G-CSF to our standard treatment for community-acquired septic shock was associated with improved hospital outcome, compared with an historical cohort of similar patients. We included all patients admitted to the Intensive Care Unit (ICU) with community-acquired septic shock between December 1998 and March 2000. Patients received 300 microg G-CSF intravenously daily for 10 days in addition to our standard treatment for community-acquired septic shock. G-CSF was discontinued early if the patient was discharged from ICU before 10 days or if the absolute neutrophil count exceeded 75 x 10(6)/mL. RESULTS: A total of 36 patients with community-acquired septic shock, an average Apache 2 score of 26.7, and a predicted mortality of 0.79, were treated with G-CSF from December 1998 to March 2000. Hospital mortality was 31% compared with an historical cohort of 11 similar patients with a hospital mortality of 73% (P = 0.018). In the subgroup of patients with melioidosis septic shock, the hospital survival improved from 5% to 100% (P < 0.0001). No significant adverse events occurred as a result of the administration of G-CSF. CONCLUSION: G-CSF is a safe adjunctive therapy in community-acquired septic shock and may be associated with improved outcome. The use of G-CSF in septic shock should undergo further investigation to define subgroups of patients who may benefit from G-CSF. The use of G-CSF in patients with septic shock due to Burkholderia pseudomallei is recommended.

Influence of isometric exercise on blood flow and sweating in glabrous and nonglabrous human skin.

The distribution of the reflex effects of isometric exercise on cutaneous vasomotor and sudomotor function is not clear. We examined the effects of isometric exercise by different muscle masses on skin blood flow (SkBF) and sweat rate (SR) in nonglabrous skin and in glabrous skin. The latter contains arteriovenous anastomoses (AVAs), which cause large fluctuations in SkBF. SkBF was measured by laser-Doppler flowmetry (LDF) and reported as cutaneous vascular conductance (CVC; LDF/mean arterial pressure). SR was measured by capacitance hygrometry. LDF and SR were measured at the sole, palm, forearm, and ventral leg during separate bouts of isometric handgrip (IHG) and isometric leg extension (ILE). CVC and its standard deviation decreased significantly during IHG and ILE in the palm and sole (P < 0.05) but not in the forearm or leg (P > 0.05). Only palmar SR increased significantly during IHG and ILE (P < 0.05). We conclude that the major reflex influences of isometric exercise on the skin include AVAs and palmar sweat glands and that this is true for both arm and leg exercise.

The influence of topical capsaicin on the local thermal control of skin blood flow in humans.

To test whether heat-sensitive receptors participate in the cutaneous vascular responses to direct heating, we monitored skin blood flow (SkBF; laser Doppler flowmetry) where the sensation of heat was induced either by local warming (T(Loc); Peltier cooling/heating unit) or by both direct warming and chemical stimulation of heat-sensitive nociceptors (capsaicin). In part I, topical capsaicin (0.075 or 0.025%) was applied to 12 cm(2) of skin 1 h before stepwise local warming of untreated and capsaicin-treated forearm skin. Pretreatment with 0.075% capsaicin cream shifted the SkBF/T(Loc) relationship to lower temperatures by an average of 6 +/- 0.8 degrees C (P < 0.05). In part II, we used a combination of topical capsaicin (0.025%) and local warming to evoke thermal sensation at one site and only local warming to evoke thermal sensation at a separate site. Cutaneous vasomotor responses were compared when the temperatures at these two sites were perceived to be the same. SkBF differed significantly between capsaicin and control sites when compared on the basis of actual temperatures, but that difference became insignificant when compared on the basis of the perceived temperatures. These data suggest heat-sensitive nociceptors are important in the cutaneous vasodilator response to local skin warming.

Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress.

It is not clear whether the diurnal variation in the cutaneous circulatory response to heat stress is via the noradrenergic vasoconstrictor system or the nonadrenergic active vasodilator system. We conducted whole body heating experiments in eight male subjects at 0630 (AM) and 1630 (PM). Skin blood flow was monitored by laser-Doppler flowmetry at control sites and at sites pretreated with bretylium (BT) to block noradrenergic vasoconstriction. Noninvasive blood pressure was used to calculate cutaneous vascular conductance. The sublingual temperature (T(or)) threshold for cutaneous vasodilation was significantly higher in PM at control and at BT-treated sites (both P < 0.01), suggesting the diurnal shift in threshold depends on the active vasodilator system. The slope of cutaneous vascular conductance as a percentage of its maximum with respect to T(or) was significantly lower in AM at control sites only. Also, in the AM, the slope at control sites was significantly lower than that at BT-treated sites (P < 0.05), suggesting that the diurnal change in the sensitivity of cutaneous vasodilation depends on vasoconstrictor system function. Overall, the diurnal variation in the reflex control of skin blood flow during heat stress involves both vasoconstrictor and active vasodilator systems.

Nonnoradrenergic mechanism of reflex cutaneous vasoconstriction in men.

We tested for a nonnoradrenergic mechanism of reflex cutaneous vasoconstriction with whole body progressive cooling in seven men. Forearm sites (<1 cm(2)) were pretreated with: 1) yohimbine (Yoh; 5 mM id) to antagonize alpha-adrenergic receptors, 2) Yoh plus propranolol (5 mM Yoh-1 mM PR id) to block alpha- and beta-adrenergic receptors, 3) iontophoretic application of bretylium tosylate (BT) to block all sympathetic vasoconstrictor nerve effects, or 4) intradermal saline. Skin blood flow was measured by laser Doppler flowmetry and arterial pressure by finger photoplethysmography; cutaneous vascular conductance (CVC) was indexed as the ratio of the two. Whole body skin temperature (T(SK)) was controlled at 34 degrees C (water-perfused suit) for 10 min and then lowered to 31 degrees C over 15 min. During cooling, vasoconstriction was blocked at BT sites (P > 0.05). CVC at saline sites fell significantly beginning at T(SK) of 33.4 +/- 0.01 degrees C (P <0.05). CVC at Yoh-PR sites was significantly reduced beginning at TSK of 33.0 +/- 0.01 degrees C (P < 0.05). After cooling, iontophoretic application of norepinephrine (NE) confirmed blockade of adrenergic receptors by Yoh-PR. Because the effects of NE were blocked at sites showing significant reflex vasoconstriction, a nonnoradrenergic mechanism in human skin is indicated, probably via a sympathetic cotransmitter.

Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature.

In a prospective study of melioidosis in northern Australia, 252 cases were found over 10 years. Of these, 46% were bacteremic, and 49 (19%) patients died. Despite administration of ceftazidime or carbapenems, mortality was 86% (43 of 50 patients) among those with septic shock. Pneumonia accounted for 127 presentations (50%) and genitourinary infections for 37 (15%), with 35 men (18%) having prostatic abscesses. Other presentations included skin abscesses (32 patients; 13%), osteomyelitis and/or septic arthritis (9; 4%), soft tissue abscesses (10; 4%), and encephalomyelitis (10; 4%). Risk factors included diabetes (37%), excessive alcohol intake (39%), chronic lung disease (27%), chronic renal disease (10%), and consumption of kava (8%). Only 1 death occurred among the 51 patients (20%) with no risk factors (relative risk, 0.08; 95% confidence interval, 0.01-0.58). Intensive therapy with ceftazidime or carbapenems, followed by at least 3 months of eradication therapy with trimethoprim-sulfamethoxazole, was associated with decreased mortality. Strategies are needed to decrease the high mortality with melioidosis septic shock. Preliminary data on granulocyte colony-stimulating factor therapy are very encouraging.

Influence of female reproductive hormones on local thermal control of skin blood flow.

Progesterone and estrogen modify thermoregulatory control such that, when both steroids are elevated, body temperature increases and the reflex thermoregulatory control of cutaneous vasodilation is shifted to higher internal temperatures. We hypothesized that the influence of these hormones would also include effects on local thermal control of skin blood flow. Experiments were conducted in women in high-hormone (HH) and low-hormone (LH) phases of oral contraceptive use. Skin blood flow was measured by laser-Doppler flowmetry, and local temperature (T(loc)) was controlled over 12 cm(2) around the sites of blood flow measurement. T(loc) was held at 32 degrees C for 10-15 min and was then decreased at one site from 32 to 20 degrees C in a ramp over 20 min. Next, T(loc) was increased from 32 to 42 degrees C in a ramp over 15 min at a separate site. Finally, T(loc) at both sites was held at 42 degrees C for 30 min to elicit maximum vasodilation; data for cutaneous vascular conductance (CVC) are expressed relative to that maximum. Whole body skin temperature (T(sk)) was held at 34 degrees C throughout each study to minimize reflex effects from differences in T(sk) between experiments. Baseline CVC did not differ between phases [8.18 +/- 1.38 (LH) vs. 8. 41 +/- 1.31% of maximum (HH); P > 0.05]. The vasodilator response to local warming was augmented in HH (P < 0.05, ANOVA). For example, at T(loc) of 40-42 degrees C, CVC averaged 76.41 +/- 3.08% of maximum in HH and 67.71 +/- 4.43% of maximum in LH (P < 0.01 LH vs. HH). The vasoconstrictor response to local cooling was unaffected by phase (P > 0.05). These findings indicate that modifications in cutaneous vascular control by female steroid hormones include enhancement of the vasodilator response to local warming and are consistent with reports of the influence of estrogen to enhance nitric oxide-dependent vasodilator responses.

Muscle metaboreceptor modulation of cutaneous active vasodilation.

PURPOSE: Isometric handgrip exercise in hyperthermia has been shown to reduce cutaneous vascular conductance (CVC) by inhibiting the cutaneous active vasodilator system. METHODS: To identify whether this response was initiated by muscle metaboreceptors, in seven subjects two 3-min bouts of isometric handgrip exercise in hyperthermia were performed, followed by 2 min of postexercise ischemia (PEI). An index of forearm skin blood flow (laser-Doppler flowmetry) was measured on the contralateral arm at an unblocked site and at a site at which adrenergic vasoconstrictor function was blocked via bretylium iontophoresis to reveal active cutaneous vasodilator function unambiguously. Sweat rate was measured via capacitance hygrometry, CVC was indexed from the ratio of skin blood flow to mean arterial pressure and was expressed as a percentage of maximal CVC at that site. In normothermia, neither isometric exercise nor PEI affected CVC (P > 0.05). RESULTS: The first bout of isometric handgrip exercise in hyperthermia reduced CVC at control sites and this reduction persisted through PEI (pre-exercise: 59.8 +/- 5.4, exercise: 49.8 +/- 4.9, PEI: 49.7 +/- 5.3% of maximum; both P < 0.05), whereas there were no significant changes in CVC at the bretylium treated sites. The succeeding bout of isometric exercise in hyperthermia significantly reduced CVC at both untreated (pre-exercise: 59.0 +/- 4.8, exercise: 47.3 +/- 4.0, PEI: 50.1 +/- 4.1% of maximum; both P < 0.05) and bretylium treated sites (pre-exercise: 61.4 +/- 7.3, exercise: 50.6 +/- 5.1, PEI: 53.9 +/- 6.0% of maximum, both P < 0.05). At both sites, CVC during PEI was lower than during the pre-exercise period (P < 0.05). Sweat rate rose significantly during both bouts of isometric exercise and remained elevated during PEI. CONCLUSIONS: These data suggest that the reduction in CVC during isometric exercise in hyperthermia, including the inhibition of the active vasodilator system, is primarily mediated by muscle metaboreceptors, whereas central command or muscle mechanoreceptors have less influence.

Effect of oral creatine ingestion on parameters of the work rate-time relationship and time to exhaustion in high-intensity cycling.

The relationship between work rate (W) and time to exhaustion (t) during intense exercise is commonly described by either a hyperbolic function (NLin), t= W'/(W-Wcp), or by its linear equivalent (LinW) Wlim=W' + Wcp(t). The parameter Wcp (critical power) has been described as an inherent characteristic of the aerobic energy system, while W' has been shown to be a ralid estimate of anaerobic work capacity. Recent studies have demonstrated that oral supplementation of creatine monohydrate (CrH2O) increases total muscle creatine stores, and have linked these increases to improved performances in intense intermittent exercise. This study was conducted to determine the effect of CrH2O supplementation on estimates of W' and Wcp derived from the NLin and LinW equations, and to determine the effect of CrH2O on t in exhaustive constant power exercise of different intensities. Fifteen active but untrained university students completed three phases of testing on a cycle ergometer: (1) familiarization, three learning trials, (2) baseline determination of W' and Wcp, four bouts performed at a W selected to elicit fatigue in 90-600 s, and (3) experimental determination of W' and Wcp, four bouts performed at the same W as baseline, but performed after 5 days of ingesting either a placebo (4 x 6 g of glucose/day) or CrH2O (4 x 5 g of CrH2O and 1 g glucose/day). Testing was administered in a double-blind manner. Analyses of covariance revealed a significant effect for CrH2O on both estimates of W' (NLin, P=0.04; LinW, P < 0.01), but not on estimates of Wcp (NLin, P=0.37; LinW; P=0.30). Within groups, t was significantly different for only CrH2O at the two highest Ws (P=0.04). It is concluded that oral ingestion of CrH2O increases estimates of W' due to an improved t at the shorter, more intense exercise bouts.

Facial cooling-induced bradycardia: attenuating effect of central command at exercise onset.

Facial cooling (FC) elicits a marked bradycardia at rest that appears to be reduced during exercise. This study was done to delineate the effects of exercise mediated central command from those of muscle afferent feedback and sympathetic stimulation on the attenuation of the bradycardic effect of FC during the onset of exercise. Ten healthy subjects (26 +/- 2 yr) were exposed to FC under five different conditions: 1) seated rest on the cycle ergometer, 2) onset of mild exercise (resting HR + 20 beats.min-1), 3) onset of moderate exercise (resting HR + 50 beats.min-1), 4) seated rest on the ergometer during electrical stimulation, and 5) seated rest on the ergometer during a cold immersion test (CT) (one hand immersed in an ice slurry at 0 degree C). The two exercise intensities were presumed to provide different degrees of central command. Electrical stimulation of the quadriceps was assumed to provide isolated muscle afferent feedback, while the CT served as a sympathetic stimulus. Beat-by-beat data were recorded for HR and mean arterial blood pressure for the duration of each test (50 s), and a rating of perceived pain was taken after each FC. FC elicited significant increases in mean arterial pressure during mild and moderate exercise compared with resting control (P < 0.05) and during moderate exercise compared to exercise without FC (P < 0.05). Mean decreases in HR during FC were similar for resting control (-12 +/- 3 beats.min-1), electrical stimulation (-10 +/- 3 beats.min-1), and CT (-9 +/- 3 beats.min-1). The HR response to FC during mild exercise (-7 +/- 2 beats.min-1) was significantly different (P < 0.05) from the rest condition; however, there was no significant bradycardia (-2 +/- 2 beats.min-1; P > 0.05) during onset of moderate exercise. These findings suggest that the magnitude of cold face-induced bradycardia may be attenuated at exercise onset by neural signals related to the higher levels of central motor command associated with heavier exercise.