Lars Lindstrom

Neural control of mechanical ventilation in respiratory failure

Mechanical ventilation is a life-saving intervention for the management of acute respiratory failure. Its objective is to reduce excessive respiratory effort while improving gas exchange. By applying positive pressure to the airway, the mechanical ventilator assumes to a varying extent the work necessary to breathe, thereby unloading the respiratory muscles. In its most basic form, called controlled mechanical ventilation, a pre-set tidal volume is delivered at a fixed rate, irrespective of the patient’s own breathing pattern. If the mechanical and natural respiratory cycles are not matched, however, the patient ‘fights’ the ventilator, causing discomfort, gas exchange deterioration and cardiovascular impairment 1 . To avoid discoordination between the patient and the ventilator, it is often necessary to suppress the patient’s intrinsic respiratory drive with the use of hyperventilation, sedation or even muscle paralysis, which increase the risk of complications due to excessive ventilation 2‐3 , drug-related adverse effects

Effects of diaphragm shortening on the mean action potential conduction velocity in canines.

1. The present study was designed to test if the mean muscle fibre action potential conduction velocity (VAPC) in the costal diaphragm changes with muscle length, in spontaneously breathing mongrel dogs. 2. VAPC was determined by the electromyogram (EMG) power spectrum ‘dip’ method, which is based on the bipolar electrode transfer function. A bipolar EMG electrode with a 20 mm fixed interelectrode distance was sutured to the costal diaphragm in the fibre direction, and in a region with a low density of motor endplates. Diaphragm length was measured with piezoelectric crystals positioned next to the EMG electrode. Seven dogs were vagotomized and spinally anaesthetized in order to increase diaphragmatic shortening, reduce velocity of shortening and abolish possible cross‐talk signals from adjacent muscles. 3. Our results showed that VAPC in the canine costal diaphragm was 3.4 m s‐1 and was not significantly related to diaphragmatic shortening.

Diaphragm function in patients with cervical cord injury or prior poliomyelitis infection

Diaphragm function was evaluated in cervical cord injury patients (CCI), 1–3 years after injury (CCI1 - 3) and 10 years or more after injury (CCI⩾10), as well as in a group of prior poliomyelitis infection patients (PPI), requiring intermittent positive pressure ventilation (IPPV) for about 6 h per night. Measurements included transdiaphragmatic pressure swings (ΔPdi) at rest, during maximal inspiratory efforts against closed airways (ΔPdimax) and during sniff manoeuvres (ie maximal inhalation through the nose, ΔPdisniff), vital capacity normalized to age and height (VC%), tidal volume (Vt), relative inspiratory time (Ti/Ttot), breathing frequency (fb), and the tension-time index of the diaphragm (TTdi = ΔPdi/ΔPdimax χ Ti/Ttot). The median VC%pred was 50% in the CCI1-3 group and 57% in the CCI≥10 group, but only 28% in the PPI group. APdimax values were similar for the CCI1-3 (11.8 kPa) and CCI≥10 (11.9 kPa) groups, but were lower (7.1 kPa) in the PPI group. Due to the reduction in ΔPdimax, the PPI group had higher ΔPdi/ΔPdimax values than the CCI groups, however, the TTdi was similar amongst the different groups studied. A submaximal exercise test in five cervical cord injury patients and in five polio patients with similar ΔPdimax, ΔPdisniff and TTdi values at rest revealed clear group differences with respect to force development, in that CCI patients showed significant increases in TTdi, while PPI demonstrated only minor changes. In CCI patients, an increase in ventilation was accompanied by an increase in ΔPdi/ΔPdimax while in contrast, the PPI patients showed no increase in ΔPdi/ΔPdimax. We conclude that CCI patients, both recently and previously injured, have a similar maximal inspiratory force and are less impaired than the PPI patients. The TTdi at rest is similar in all groups, but the PPI patients react to inspiratory loads with little increases in TTdi, while the CCI patients increase their TTdi above fatiguing (0.15) levels. The different behaviours may be linked to loss of sensory pathways in the CCI patients.

Electromyographical evidence for exercise-induced diaphragm fatigue in patients with chronic cervical cord injury or prior poliomyelitis infection

The purpose of this study was to determine, in exercising patients, how much diaphragm force increases before electromyographical evidence of diaphragm fatigue occurs. The study was performed in ten male patients with complete cervical cord injury (CCI) at the C5 to C8 levels, and five male patients with prior poliomyelitis infection (PPI) requiring chronic treatment with intermittent positive pressure ventilation (IPPV) at night. We studied the time course of the diaphragmatic tension-time index (TTdi), the centre frequency (CFdi) of the diaphragm electromyogram (EMGdi) power spectrum, and the ventilatory parameters, during steadystate submaximal arm/leg exercise.During exercise, early signs of diaphragm fatigue were present in seven out of 10 CCI patients and in four out of five PPI patients, as indicated by a reduction in CFdi. The increase in TTdi achieved before reductions in CFdi occurred was twofold in both the CCI and PPI patients. All patients except for the PPI patients, who demonstrated a reduction in CFdi, showed an increase in minute ventilation (VE), achieved by increasing both their tidal volume (Vt) and the breathing frequency (fb). The PPI patients demonstrating reductions in CFdi during exercise also increased their VE however, this was achieved by increasing fb while Vt remained constant. Following the reductions in CFdi, the CCI patients further increased their TTdi throughout the exercise test, while the PPI patients reduced their TTdi values.In conclusion: (1) During exercise, electromyographical evidence for diaphragmatic fatigue frequently occurred in the CCI and PPI patients studied; (2) Compared to the eightfold increase in TTdi seen in healthy subjects before reductions in CFdi occur, the TTdi values increased only two-fold before electromyographical evidence of diaphragm fatigue was present in these patients; (3) There is a clear discrepancy between the CCI and PPI patients who demonstrate electromyographical evidence of diaphragm fatigue, in terms of their ventilatory and TTdi responses.

Effect of increased diaphragm activation on diaphragm power spectrum center frequency

Increased transdiaphragmatic pressure, reduced muscle blood flow, and increased duty cycle have all been associated with a reduction in the center frequency (CFdi) of the diaphragms electrical activity (EAdi). However, the specific influence of diaphragm activation on CFdi is unknown. We evaluated whether increased diaphragm activation would result in a greater decline in the CFdi when pressure-time product (PTPdi) was kept constant. Five healthy subjects performed periods of intermittent quasi-static diaphragmatic contractions with a fixed duty cycle. In separate runs, subjects targeted transdiaphragmatic pressures (Pdi) by performing end-inspiratory holds with the glottis open and expulsive maneuvers at end-expiratory lung volume (EELV). Diaphragm activation and pressures were measured with an electrode array and balloons mounted on an esophago-gastric catheter, respectively. The EAdi, which was 25+/-8%(S.D.) of maximum at EELV, increased to 61+/-8% (P<0.001) when an identical Pdi (averaging 31+/-13 cmH2O) was generated at a higher lung volume (77% of inspiratory capacity). The latter was associated with a 17% greater decline in CFdi (P=0.012). In order to reproduce at EELV, the decrease in CFdi observed at the increased lung volume, a two-fold increase in PTPdi was required. We conclude that CFdi responds specifically to increased diaphragm activation when pressure-time product remains constant.

Electromyographic registration of diaphragmatic fatigue during sustained trunk flexion in cervical cord injured patients

When performing forward trunk flexion, cervical cord injured (CCI) patients exhibit continuous and high EMG activity in the diaphragm and elevated abdominal pressures. This study addressed the question whether the trunk flexion manoeuvres cause such a high force development in the diaphragm that this muscle shows EMG signs of fatigue.Six patients with complete cervical cord lesions were tested sitting in their own wheelchairs. The tension-time indices obtained when patients were sitting in a relaxed position were moderately to markedly higher than in normal subjects. The force developed during trunk flexion averaged 30% of the maximal transdiaphragmatic pressure and was accompanied by clear EMG findings of diaphragmatic fatigue in all patients except one.The acute diaphragmatic load in certain CCI patients may well produce ischaemia and increase the risk of tissue impairment. Therefore, there appears to be a need for differing strategies in the short and in the long term treatment of CCI patients; longitudinal evaluation of main diaphragmatic function may be useful for an adequate amount of respiratory muscle training.

Influence of atracurium on the diaphragm mean action potential conduction velocity in canines.

BACKGROUND It has been shown that progressive neuromuscular blockade (NMB) affects the electromyogram power spectrum and compound muscle action potential duration in skeletal muscle. These measures are linked to the mean muscle action potential conduction velocity (APCV), but no studies have confirmed a relation between the mean APCV and NMB. The aim of this study was to determine whether diaphragm mean APCV is affected by NMB. METHODS The effects of NMB on diaphragm mean APCV were evaluated in five mongrel dogs. Progressive NMB was induced by slow intravenous infusion of atracurium. During spontaneous breathing, the diaphragm mean APCV was determined by electromyogram signals, in the time and frequency domains. The magnitude of NMB was quantified by the amplitude of the compound muscle action potential and by changes in muscle shortening during supramaximal stimulation of the phrenic nerve. RESULTS Progressive NMB was associated with a decrease in diaphragm mean APCV. At approximately 70% reduction in the compound muscle action potential amplitude, diaphragm mean APCV had decreased more than 20%. Recovery after NMB was characterized by a restoration of the mean APCV to control values. CONCLUSION This study shows that progressive NMB paralyzes motor units within the diaphragm in an orderly manner, and the blockade first affects muscle fibers with high APCV before it affects fibers with lower APCV.