C H Hamnegard

Proportional assist ventilation as an aid to exercise training in severe chronic obstructive pulmonary disease

Background: The effects of providing ventilatory assistance to patients with severe chronic obstructive pulmonary disease (COPD) during a high intensity outpatient cycle exercise programme were examined. Methods: Nineteen patients (17 men) with severe COPD (mean (SD) forced expiratory volume in 1 second (FEV1) 27 (7)% predicted) underwent a 6 week supervised outpatient cycle exercise programme. Ten patients were randomised to exercise with ventilatory assistance using proportional assist ventilation (PAV) and nine (two women) to exercise unaided. Before and after training patients performed a maximal symptom limited incremental cycle test to determine peak work rate (Wpeak) followed by a constant work rate (CWR) test at 70% of Wpeak achieved in the baseline incremental test. Minute ventilation (Ve), heart rate, and arterialised venous plasma lactate concentration [La+] were measured before and after each test. Results: Mean training intensity (Wt/Wpeak) at 6 weeks was 15.2% (95% CI 3.2 to 27.1) higher in the group that used ventilatory assistance (p=0.016). Peak work rate after training was 18.4% (95% CI 6.4 to 30.5) higher (p=0.005) in the assisted group (p=0.09). [La+] at an identical workload after training was reduced by 30% (95% CI 16 to 44) in the assisted group (p=0.002 compared with baseline) and by 11% (95% CI –7 to 31) (p=0.08 compared with baseline) in the unassisted group (mean difference 18.4% (95% CI 3.3 to 40), p=0.09). A significant inverse relationship was found between reduction in plasma lactate concentration (ΔL) at an equivalent workload after training during the CWR test and Wt/Wpeak achieved during the last week of training (r=–0.7, p=0.0006). Conclusions: PAV enables a higher intensity of training in patients with severe COPD, leading to greater improvements in maximum exercise capacity with evidence of true physiological adaptation.

Potentiation of diaphragmatic twitch after voluntary contraction in normal subjects.

BACKGROUND--Skeletal muscle twitch responses may be transiently increased by previous contractions, a phenomenon termed twitch potentiation. The aim of this study was to examine the extent and time course of diaphragmatic twitch potentiation and its relationship to both the magnitude and duration of the preceding voluntary diaphragmatic contraction. METHODS--Twitch transdiaphragmatic pressure (PDI) was measured in six normal subjects, before and after voluntary diaphragm contractions of 100%, 75%, 50%, and 25% of maximum PDI (PDImax) sustained for five and 10 seconds. RESULTS--Twitch PDI was significantly increased after 100%, 75%, and 50% contractions. Following maximal contractions sustained for 10 seconds the mean increase in twitch PDI was 52%. Following 50% contractions sustained for five seconds the mean increase in twitch height was 28%. In all runs twitch PDI returned to rested levels within 20 minutes. CONCLUSIONS--Twitch potentiation can be substantial, even following submaximal contractions, and must be taken into account when twitch pressure is used to assess diaphragm contractility.

Portable measurement of maximum mouth pressures

We have compared a small portable mouth pressure meter (MPM) to our laboratory standard (LS) pressure recording equipment in order to evaluate this new device. The mouth pressure meter measures and displays as a digital read-out peak pressure for inspiratory and expiratory efforts. It samples the signal at 16 Hz, and an integral microprocessor is programmed to determine and display the maximum pressure averaged over one second both during inspiratory and expiratory manoeuvres (PImax and PEmax, respectively). A fine bore catheter connecting the mouthpiece of the mouth pressure meter to a Validyne pressure transducer enabled simultaneous measurement of pressure, which was analysed by LabVIEW, running on a Macintosh Quadra 700 computer. We studied 13 normal subjects and 11 patients with respiratory disease. Each subject performed inspiratory and five expiratory efforts. The values displayed from the mouth pressure meter were manually recorded. The mouth pressure meter reliably and accurately measured peak pressure and maximal pressure both for inspiratory and expiratory efforts in normals and patients. The mean +/- SD difference when compared with the Validyne method was 0.19 +/- 0.12 and -0.04 +/- 0.12 kPa, for PImax and PEmax, respectively. This portable device should be useful to measure mouth pressures, not only in the routine lung function laboratory but also at the bedside and in the clinic.

Unilateral magnetic stimulation of the phrenic nerve.

BACKGROUND--Electrical stimulation of the phrenic nerve is a useful non-volitional method of assessing diaphragm contractility. During the assessment of hemidiaphragm contractility with electrical stimulation, low twitch transdiaphragmatic pressures may result from difficulty in locating and stimulating the phrenic nerve. Cervical magnetic stimulation overcomes some of these problems, but this technique may not be absolutely specific and does not allow the contractility of one hemidiaphragm to be assessed. This study assesses both the best means of producing supramaximal unilateral magnetic phrenic stimulation and its reproducibility. This technique is then applied to patients. METHODS--The ability of four different magnetic coils to produce unilateral phrenic stimulation in five normal subjects was assessed from twitch transdiaphragmatic pressure (TwPDI) measurements and diaphragmatic electromyogram (EMG) recordings. The results from magnetic stimulation were compared with those from electrical stimulation. To determine whether the magnetic field affects the contralateral phrenic nerve as well as the intended phrenic nerve, EMG recordings from each hemidiaphragm were compared during stimulation on the same side and the opposite side relative to the recording electrodes. The EMG recordings were made from skin surface electrodes in five normal subjects and from needle electrodes placed in the diaphragm during cardiac surgery in six patients. Similarly, the direction of hemidiaphragm movement was evaluated by ultrasonography. To determine the usefulness of the technique in patients the 43 mm mean diameter double coil was used in 54 patients referred for assessment of possible respiratory muscle weakness. These results were compared with unilateral electrical phrenic stimulation, maximum sniff PDI, and TwPDI during cervical magnetic stimulation. RESULTS--In the five normal subjects supramaximal stimulation was established for eight out of 10 phrenic nerves with the 43 mm double coil. Supramaximal unilateral magnetic stimulation produced a higher TwPDI than electrical stimulation (mean (SD) 13.4 (2.5) cm H2O with 35 mm coil; 14.1 (3.8) cm H2O with 43 mm coil; 10.0 (1.7) cm H2O with electrical stimulation). Spread of the magnetic field to the opposite phrenic nerve produced a small amplitude contralateral diaphragm EMG measured from skin surface electrodes which reached a mean of 15% of the maximum EMG amplitude produced by ipsilateral stimulation. Similarly, in six patients with EMG activity recorded directly from needle electrodes, the contralateral spread of the magnetic field produced EMG activity up to a mean of 3% and a maximum of 6% of that seen with ipsilateral stimulation. Unilateral magnetic stimulation of the phrenic nerve was rapidly achieved and well tolerated. In the 54 patients unilateral magnetic TwPDI was more closely related than unilateral electrical TwPDI to transdiaphragmatic pressure produced during maximum sniffs and cervical magnetic stimulation. Unilateral magnetic stimulation eliminated the problem of producing a falsely low TwPDI because of technical difficulties in locating and adequately stimulating the nerve. Eight patients with unilateral phrenic nerve paresis, as indicated by a unilaterally elevated hemidiaphragm on a chest radiograph and maximum sniff PDI consistent with hemidiaphragm weakness, were all accurately identified by unilateral magnetic stimulation. CONCLUSIONS--Unilateral magnetic phrenic nerve stimulation is easy to apply and is a reproducible technique in the assessment of hemidiaphragm contractility. It is well tolerated and allows hemidiaphragm contractility to be rapidly and reliably assessed because precise positioning of the coils is not necessary. This may be particularly useful in patients. In addition, the anterolateral positioning of the coil allows the use of the magnet in the supine patient such as in the operating theatre or intensive care unit.

Diaphragm fatigue following maximal ventilation in man

When highly motivated normal subjects perform maximal isocapnic ventilation, a substantial fall in ventilation is observed during the first minute associated with slowing of the maximum relaxation rate (MRR) of the inspiratory muscles. This suggests that these muscles are excessively loaded, raising the possibility that overt contractile failure of the diaphragm contributes to the fall in ventilation. We therefore investigated the effect of maximal isocapnic ventilation (MIV) on twitch transdiaphragmatic pressure (Pdi,Tw) elicited by cervical magnetic stimulation. We measured Pdi,Tw before and after 2 min MIV in nine normal subjects. Initial mean (SD) ventilation for the nine subjects was 196 (15) L.min-1 falling by 35% at 1 min. Pdi,Tw fell following MIV, at 10 min was reduced by 24%, and remained substantially reduced 90 min after MIV. No change in Pdi,Tw was observed during control studies in which subjects were studied with the same protocol but omitting MIV. We conclude that diaphragmatic contractility is reduced after 2 min maximal isocapnic ventilation and diaphragmatic fatigue may be a limiting factor in maximal ventilation in man.

Measurement of sniff nasal and diaphragm twitch mouth pressure in patients.

BACKGROUND: Inspiratory muscle weakness is a recognised cause of unexplained dyspnoea. It may be suggested by the finding of a low static inspiratory mouth pressure (MIP), but MIP is a difficult test to perform, with a wide normal range; a low MIP may also occur if the patient has not properly performed the manoeuvre. Further investigation conventionally requires balloon catheters to obtain oesophageal (Poes) and transdiaphragmatic pressure (Pdi) during sniffs or phrenic nerve stimulation. Two non-invasive tests of inspiratory muscle strength have recently been described--nasal pressure during a maximal sniff (Sn Pnas) and mouth pressure during magnetic stimulation of the phrenic nerves (Tw Pmo). The use of these two tests in combination might identify patients without inspiratory muscle weakness who are unable to produce a satisfactory MIP< therefore avoiding the need for investigation with balloon catheters. METHODS: Thirty consecutive patients with clinically suspected inspiratory muscle weakness and a low MIP underwent both conventional (Sn Poes and Tw Pdi) and non-invasive testing (Sn Pnas and Tw Pmo). Weakness was considered to be excluded by a Sn Poes of > or = 80 cm H20 or a Tw Pdi of > or = 20 cm H20. The limit values used to test the hypothesis were Sn Pnas > or = 70 cm H20 or Tw Pmo > or = 12 cm H20. RESULTS: Inspiratory muscle weakness was excluded in 17 of the 30 patients. Fifteen of these would have been identified using Sn Pnas and Tw Pmo, with better results when the two tests were combined. The cut off values selected for Sn Pnas and Tw Pmo were shown by ROC plots to indicate normal strength conservatively, avoiding failure to detect mild degrees of weakness. No patient with global weakness was considered normal by Sn Pnas or Tw Pmo. CONCLUSIONS: In most patients with normal inspiratory strength and a low MIP, Tw Pmo and Sn Pnas used in combination can reliably exclude global inspiratory muscle weakness, reducing the number of patients who need testing with balloon catheters.

Anterior magnetic phrenic nerve stimulation: laboratory and clinical evaluation

Objective: Anterior magnetic stimulation (aMS) of the phrenic nerves is a new method for the assessment of diaphragm contractility that might have particular applications for the clinical assessment of critically ill patients who are commonly supine. Design: We compared aMS with existing techniques for measurement of diaphragm weakness and fatigue in 10 normal subjects, 27 ambulant patients with suspected diaphragm weakness and 10 critically ill patients. Setting: Laboratory and intensive care unit of two university hospitals. Results: Although aMS was not demonstrably supramaximal in normal subjects, the mean value of twitch transdiaphragmatic pressure (Tw Pdi) obtained at 100 % of stimulator output, 23.7 cmH2O, did not differ significantly from that obtained with bilateral supramaximal electrical stimulation (ES), 24.9 cmH2O, or bilateral anterior magnetic phrenic nerve stimulation (BAMPS), 27.3 cmH2O. A fatiguing protocol produced a 20 % fall in aMS-Tw Pdi and a 19 % fall in BAMPS-Tw Pdi; the fall in aMS-Tw Pdi correlated with the fall in BAMPS-Tw Pdi (r2 = 0.84, p = 0.03) indicating that aMS can detect diaphragm fatigue. In ambulant patients aMS agreed closely with existing measures of diaphragm strength. The maximal sniff Pdi correlated with both the aMS-Tw Pdi (r2 = 0.60, p < 0.0001) and the BAMPS-Tw Pdi (r2 = 0.65, p < 0.0001) and the aMS-Tw Pdi was a mean (SD) 2.2 (4.3) cmH2O less than BAMPS-Tw Pdi. In addition, aMS correctly identified diaphragm dysfunction in patients studied on the ICU. Conclusions: We conclude that aMS is of clinical value for the investigation of suspected diaphragm weakness.

Clinical assessment of diaphragm strength by cervical magnetic stimulation of the phrenic nerves.

BACKGROUND: Accurate assessment of diaphragm strength can be difficult. Transdiaphragmatic pressure (PDI) measurements during volitional manoeuvres are useful but it may be difficult to ensure maximum patient effort. Magnetic stimulation of the phrenic nerves is easy to perform and the results are reproducible in normal subjects. The purpose of the present study was to evaluate the usefulness of magnetic stimulation of the phrenic nerves in the assessment of diaphragm weakness in patients. METHODS: Sixty-six patients referred for assessment of respiratory muscle strength and 23 normal subjects were studied. Twitch PDI (TwPDI) following magnetic stimulation of the phrenic nerves and sniffPDI were obtained in all individuals. TWPDI following bilateral electrical stimulation of the phrenic nerves was also obtained in eight patients. RESULTS: Mean (SD) TwPdi for the normal subjects was 31 (6) cm H2O and 18 (11) cm H2O for the patients. TwPDI and sniffPDI were correlated (r = 0.77). Seven of the 37 patients (19%) with a reduced sniffPDI had a TwPDI within the normal range whereas two of the 32 patients (6%) with a reduced TwPDI had a normal sniffPDI. TwPDI was similar with magnetic and electrical stimulation. CONCLUSIONS: TwPDI following magnetic stimulation of the phrenic nerves is a clinically useful measurement when assessing diaphragm weakness.

Mechanisms of improvement of respiratory failure in patients with COPD treated with NIV

Background Noninvasive ventilation (NIV) improves gas-exchange and symptoms in selected chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure. We hypothesized NIV reverses respiratory failure by one or all of increased ventilatory response to carbon-dioxide, reduced respiratory muscle fatigue, or improved pulmonary mechanics. Methods Nineteen stable COPD patients (forced expiratory volume in one second 35% predicted) were studied at baseline (D0), 5–8 days (D5) and 3 months (3M) after starting NIV. Results Ventilator use was 6.2 (3.7) hours per night at D5 and 3.4 (1.6) at 3M (p = 0.12). Mean (SD) daytime arterial carbon-dioxide tension (PaCO2) was reduced from 7.4 (1.2) kPa to 7.0 (1.1) kPa at D5 and 6.5 (1.1) kPa at 3M (p = 0.001). Total lung capacity decreased from 107 (28) % predicted to 103 (28) at D5 and 103 (27) % predicted at 3M (p = 0.035). At D5 there was an increase in the hypercapnic ventilatory response and some volitional measures of inspiratory and expiratory muscle strength, but not isolated diaphragmatic strength whether assessed by volitional or nonvolitional methods. Conclusion These findings suggest decreased gas trapping and increased ventilatory sensitivity to CO2 are the principal mechanism underlying improvements in gas-exchange in patients with COPD following NIV. Changes in some volitional but not nonvolitional muscle strength measures may reflect improved patient effort.

Inspiratory muscle relaxation rate assessed from sniff nasal pressure.

BACKGROUND--Slowing of the maximum relaxation rate (MRR) of inspiratory muscles measured from oesophageal pressure (POES) during sniffs has been used as an index of the onset and recovery of respiratory muscle fatigue. The purpose of this study was to measure MRR at the nose (PNASAL MRR), to investigate its relationship with POES MRR, and to establish whether PNASAL MRR slows with respiratory loading. METHODS--Five normal subjects were studied. Each performed sniffs before and after two minutes of maximal isocapnic ventilation (MIV). In a separate session the subjects performed submaximal sniffs. POES and PNASAL were recorded during sniffs and the MRR (% pressure fall/10 ms) for each sniff was determined. RESULTS--Before MIV mean POES MRR was 8.9 and PNASAL MRR was 9.3. The mean (SD) difference between PNASAL MRR and POES MRR during a maximal sniff was 0.48 (0.34) (n = 64) and during submaximal sniffs was 0.28 (0.46) (n = 526). The subjects showed a mean decrease in sniff POES MRR of 27.4% (range 22.5-36%) after MIV and a similar reduction in sniff PNASAL MRR of 28.5% (range 24.1-41.3%). Both returned to control values within 5-10 minutes. CONCLUSIONS--PNASAL MRR reflects POES MRR over a wide range of sniff pressures, PNASAL MRR of maximal sniffs reflects POES MRR in normal subjects at rest and following MIV, so measurement of PNASAL MRR may be a useful non-invasive method for measuring inspiratory muscle MRR, thereby providing an index of respiratory muscle fatigue.