Contractile properties of the human diaphragm during chronic hyperinflation

BACKGROUND. In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. METHODS. In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). RESULTS. At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). CONCLUSIONS. The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.     

Reproducibility of twitch and sniff transdiaphragmatic pressures

Twitch transdiaphragmatic pressure (Tw Pdi) measured with magnetic stimulation of the phrenic nerve is used to follow up patients and to assess the effect of clinical treatments on diaphragm function. However the reproducibility of Tw Pdi on different occasions has been little studied. We investigated 32 normal subjects, measuring Tw Pdi elicited by bilateral magnetic stimulation of the phrenic nerves on two to 14 occasions. Sniff transdiaphragmatic pressure (sniff Pdi) was also measured. The mean value of Tw Pdi and sniff Pdi were 28+/-5 and 134+/-24 cm H(2)O, respectively. The within subjects coefficient of variation was 11% for both Tw Pdi and sniff Pdi. We conclude that there is a variability of Tw Pdi and the variability of Tw Pdi is the same as that of sniff Pdi.     

Maximal activation of the human diaphragm but not inspiratory intercostal muscles during static inspiratory efforts

It is widely held that transdiaphragmatic pressure is a reliable index of the extent of central activation of the diaphragm but the maximal voluntary transdiaphragmatic pressure is lower during inspiratory than expulsive efforts. To determine whether the diaphragm is fully activated during the two manoeuvres supramaximal stimuli were delivered to both phrenic nerves during maximal efforts. No discernible twitch was evoked during 30-55% of attempted maximal efforts with either voluntary manoeuvre. Thus the difference in maximal transdiaphragmatic pressure between the manoeuvres must reflect changes in chest-wall geometry or mechanics rather than in the phrenic motor outflow. Inspiratory intercostal muscle activity was consistently submaximal during maximal inspiratory efforts.     

Diaphragmatic effects of selective resection of the upper phrenic nerve root in dogs

The aim of this study was to evaluate the effects on the diaphragm of upper phrenic nerve root resections in dogs. During laryngeal reinnervation, selective resections of the upper phrenic nerve root (C5) were performed unilaterally (right side, n=7; Group A) and bilaterally (n=6; Group B) and compared to non denervated animals (n=5). After 8 months, a diaphragmatic evaluation was performed: X-ray, EMG, transdiaphragmatic pressure (Pdi) after ipsi- and bilateral tetanic stimulation of the phrenic nerves and a bilateral histological study of five hemidiaphragmatic regions. EMG alterations were significantly more severe in Group B than in Group A, for the left (p<0.05) and right hemidiaphragms (p<0.01). No differences in the X-rays were noted between the three groups. The Pdi of the three groups after occlusion and phrenic nerve stimulations (unilateral and bilateral) were not statistically different. Histological data demonstrated that there were no differences in fibre irregularity, predominant fibre type or fibrosis between the three groups. Macroscopic and microscopic atrophy, which was mainly present on the anterior regions of the hemidiaphragms, was significantly higher in Group B than in Group A and undenervated dogs (p<0.05). In conclusion, resection of the upper phrenic nerve root of one phrenic nerve (right side) have limited effect on the diaphragm in dogs. However, resection of the upper phrenic nerve root on both sides resulted in a significant effect on the EMGs and histology of the entire diaphragm without any significant consequences on transdiaphragmatic pressure.     

Transient hypoparathyroidism during acute alcohol intoxication

BACKGROUND. Persons with chronic alcoholism frequently have hypocalcemia, hypomagnesemia, and osteoporosis. The short-term effects of alcohol ingestion on calcium and magnesium metabolism are poorly understood, however. METHODS. We measured serum calcium, magnesium, and phosphate concentrations in 17 normal men and 7 normal women before and at intervals up to 16 hours after the ingestion of 1.2 to 1.5 g of alcohol per kilogram of body weight over a 3-hour period (doses sufficient to cause acute intoxication). Urinary excretion of calcium, magnesium, and phosphate and serum calciotropic hormone levels were measured in 16 of these subjects. As a control, the same measurements were made after the ingestion of fruit juice instead of alcohol. RESULTS. The mean (+/- SE) peak blood alcohol level in the men was 37.5 +/- 1.6 mmol per liter, and in the women it was 38.0 +/- 3.2 mmol per liter. In the men the mean serum parathyroid hormone concentration decreased from 16.1 +/- 2.1 to 6.8 +/- 0.9 ng per liter at the end of the three-hour drinking period. The value at this time was 30 percent of that at the end of the three-hour session during which the men drank fruit juice (P = 0.004). The serum concentration of ionized calcium reached a nadir eight hours after the beginning of alcohol administration (decreasing from 1.18 +/- 0.01 to 1.15 +/- 0.01 mmol per liter; P less than 0.001 as compared with values during the fruit-juice study), and urinary excretion of calcium increased from 0.34 +/- 0.08 to 0.36 +/- 0.08 mmol per hour (P less than 0.01 as compared with values during the fruit-juice study). Serum parathyroid hormone levels exceeded base-line values during the last 4 hours of the 16-hour study period; this increase was accompanied by a decrease in the urinary excretion of calcium. Both serum levels of magnesium (in the first 6 hours) and urinary levels (in the first 12 hours) increased after the ingestion of alcohol. In the women, serum parathyroid hormone levels decreased from 29.2 +/- 2.8 to 17.3 +/- 2.6 ng per liter two hours after the administration of alcohol was begun (P less than 0.001) and increased above base-line values during the last four hours of the study period. The serum concentration of ionized calcium decreased from 1.20 +/- 0.01 to 1.16 +/- 0.01 mmol per liter, reaching a nadir 8 to 12 hours after alcohol administration was begun (P less than 0.001). CONCLUSIONS. Short-term alcohol administration causes transitory hypoparathyroidism. This decline in the secretion of parathyroid hormone accounts at least in part for the transient hypocalcemia, hypercalciuria, and hypermagnesuria that follow alcohol ingestion.     

The effect of asymptomatic nocturnal hypoglycemia on glycemic control in diabetes mellitus

To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (+/- SE) plasma glucose level reached a nadir of 4.5 +/- 0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9 +/- 0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6 +/- 0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4 +/- 0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3 +/- 0.2 mmol per liter) and postbreakfast (12.5 +/- 0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2 +/- 0.2 mmol per liter and 8.7 +/- 0.4 mmol per liter, respectively; P less than 0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P less than 0.001), growth hormone (r = 0.57, P less than 0.009), and cortisol (r = 0.52, P less than 0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P less than 0.005). We conclude that asymptomatic nocturnal hypoglycemia can cause clinically important deterioration in glycemic control (the Somogyi phenomenon) in patients receiving intensive insulin therapy, and should therefore be considered in the differential diagnosis of unexplained morning hyperglycemia.     

Respiratory muscle injury, fatigue and serum skeletal troponin I in rat

To evaluate injury to respiratory muscles of rats breathing against an inspiratory resistive load, we measured the release into blood of a myofilament protein, skeletal troponin I (sTnI), and related this release to the time course of changes in arterial blood gases, respiratory drive (phrenic activity), and pressure generation. After ∼1.5 h of loading, hypercapnic ventilatory failure occurred, coincident with a decrease in the ratio of transdiaphragmatic pressure to integrated phrenic activity ( P _di /∫Phr) during sighs. This was followed at ∼1.9 h by a decrease in the P _di /∫Phr ratio during normal loaded breaths (diaphragmatic fatigue). Loading was terminated at pump failure (a decline of P _di to half of steady-state loaded values), ∼2.4 h after load onset. During 30 s occlusions post loading, rats generated pressure profiles similar to those during occlusions before loading, with comparable blood gases, but at a higher neural drive. In a second series of rats, we tested for sTnI release using Western blot–direct serum analysis of blood samples taken before and during loading to pump failure. We detected only the fast isoform of sTnI, release beginning midway through loading. Differential detection with various monoclonal antibodies indicated the presence of modified forms of fast sTnI. The release of fast sTnI is consistent with load-induced injury of fast glycolytic fibres of inspiratory muscles, probably the diaphragm. Characterization of released fast sTnI may provide insights into the molecular basis of respiratory muscle dysfunction; fast sTnI may also prove useful as a marker of impending respiratory muscle fatigue.     

Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease

We studied the effects of theophylline on diaphragmatic strength and fatigue in 15 patients with severe chronic obstructive pulmonary disease. Diaphragmatic strength was assessed by measurement of the transdiaphragmatic pressure generated at functional residual capacity during a maximal inspiratory effort against closed airways. Diaphragmatic fatigue was induced by resistive loaded breathing. The electrical activity of the diaphragm was recorded with an esophageal electrode during the fatigue runs, and the high-low ratio of the electrical signal was analyzed to assess diaphragmatic fatigue. Studies were performed before and after 7 and 30 days of theophylline administration (mean plasma level, 13 +/- 2 mg per liter). A control group received a placebo instead of theophylline. Theophylline increased maximal transdiaphragmatic pressure by 16 per cent after 7 days of administration (P less than 0.01), and this increase persisted after 30 days. No significant change in maximal transdiaphragmatic pressure was observed in the group given the placebo. Theophylline also suppressed diaphragmatic fatigue in all patients who received it. We conclude that theophylline has a potent and long-lasting effect on diaphragmatic strength and fatigue in patients with fixed airway obstruction.     

Abnormalities in parathyroid hormone secretion and 1,25-dihydroxyvitamin D3 formation in women with osteoporosis

We investigated the parathyroid hormone-1,25-dihydroxyvitamin D3 (1,25(OH)2D) axis in osteoporosis by administering phosphate to 8 postmenopausal women with osteoporosis (49 to 78 years old) and to 10 normal women matched for age (50 to 74 years). All subjects responded with a similar increase in the serum phosphorus concentration (women with osteoporosis, 1.15 +/- 0.06 to 1.79 +/- 0.09 mmol per liter; controls, 1.14 +/- 0.05 to 1.73 +/- 0.08 mmol per liter) and a fall in the ionized calcium concentration (women with osteoporosis, 1.12 +/- 0.03 to 1.06 +/- 0.03 mmol per liter; controls, 1.17 +/- 0.01 to 1.11 +/- 0.02 mmol per liter). Parathyroid hormone levels rose 2.5-fold in the control group (15.4 +/- 2.2 to 37.9 +/- 6.1 pg per milliliter) but increased by only 43 percent in the group with osteoporosis (14.8 +/- 2.8 to 21.2 +/- 4.1 pg per milliliter), an increase similar to that previously reported in young normal subjects (53 percent). In healthy older and younger subjects, the levels of 1,25(OH)2D did not change; in the subjects with osteoporosis, however, they decreased significantly (50 percent). We conclude that older women require a greater parathyroid hormone stimulus than younger women to maintain vitamin D homeostasis, because of an age-related decline in the formation of 1,25(OH)2D in response to parathyroid hormone, and that in osteoporosis the age-appropriate parathyroid hormone response to the same hypocalcemic signal is diminished. Our results are consistent with the presence of an abnormality in parathyroid hormone secretory function in osteoporosis in addition to the universal decline in 1,25(OH)2D responsiveness associated with aging.     

Post-exercise diaphragm shielding: a novel approach to exercise-induced diaphragmatic fatigue

Based on the "post-exercise diaphragm shielding" hypothesis this study tested whether both diaphragmatic force-generation (DFG) and diaphragmatic fatigue (DF) remain unchanged during consecutive exercise-trials. Twelve subjects ( [Formula: see text] 58.4+/-6.6mlkg(-1)min(-1)) performed three consecutive exercise-trials (T(alpha)/T(beta)/T(gamma); workload(max) 85% [Formula: see text] ) each followed by recovery (6min). Twitch transdiaphragmatic pressure during supramaximal magnetic phrenic nerve stimulation (TwPdi, every 30s), ratings of perceived exertion (RPE, every 90s) and ergospirometric data (continuously) were assessed throughout the entire protocol (46.5min). DFG and DF did not differ among all trials (TwPdi-baseline: 2.2+/-0.7kPa; TwPdi-peak: T(alpha)/T(beta)/T(gamma) 3.1+/-0.7kPa vs 3.0+/-0.8kPa vs 3.2+/-0.8kPa; TwPdi-bottom: T(alpha)/T(beta)/T(gamma) 1.9+/-0.6kPa vs 2.0+/-0.7kPa vs 1.8+/-0.5kPa, both p>0.4, RM-ANOVA). Furthermore, TwPdi revealed close relationships with RPE (r=0.91, p<0.0001) and oxygen uptake (r=0.94, p<0.0001) during exercise. In conclusion, both DFG (baseline-to-peak) and DF (baseline-to-bottom) achieve similar magnitudes during and after consecutive exercise-trials and are closely linked to RPE and oxygen uptake. This suggests that DF neither reflects impaired diaphragmatic function nor impairs exercise performance; rather it is likely to reflect post-exercise diaphragm shielding.     

Restoration of respiratory muscle function following spinal cord injury. Review of electrical and magnetic stimulation techniques

Respiratory complications are a leading cause of morbidity and mortality in patients with spinal cord injury. Several techniques, currently available or in development, have the capacity to restore respiratory muscle function allowing these patients to live more normal lives and hopefully reduce the incidence of respiratory complications. Bilateral phrenic nerve pacing, a clinically accepted technique to restore inspiratory muscle function, allows patients with ventilator dependent tetraplegia complete freedom from mechanical ventilation. Compared to mechanical ventilation, phrenic nerve pacing provides patients with increased mobility, improved speech, improved comfort level and reduction in health care costs. The results of clinical trials of laparoscopically placed intramuscular diaphragm electrodes suggest that diaphragm pacing can also be achieved without the need for a thoracotomy and associated long hospital stay, and without manipulation of the phrenic nerve which carries a risk of phrenic nerve injury. Other clinical trials are being performed to restore inspiratory intercostal function. In patients with only unilateral phrenic nerve function who are not candidates for phrenic nerve pacing, combined intercostal and unilateral diaphragm pacing appears to provide benefits similar to that of bilateral diaphragm pacing. Clinical trials are also underway to restore expiratory muscle function. Magnetic stimulation, surface stimulation and spinal cord stimulation of the expiratory muscles are promising techniques to restore an effective cough mechanism in this patient population. These techniques hold promise to reduce the incidence of respiratory tract infections, atelectasis and respiratory failure in patients with spinal cord injury and reduce the morbidity and mortality associated with these complications.     

Cartography of human diaphragmatic innervation: preliminary data

In humans, anatomy indicates that the phrenic nerve mainly arises from the C4 cervical root, with variable C3 and C5 contributions. How this translates into functional innervation is unknown. The diaphragm response to electrical stimulation of C3, C4 and C5 was described in three patients undergoing surgical laryngeal reinnervation with an upper phrenic root (surface chest electrodes at anterior, lateral and posterior sites; oesophageal and gastric pressures (Pes and Pga) to derive transdiaphragmatic pressure (Pdi)). Anatomically, the phrenic nerve predominantly originated from C4. Phrenic stimulation elicited motor responses at the three sites in the three patients, as did C4 stimulation. It produced Pdi values of 9, 11, and 14cmH(2)O in the three patients, respectively, vs. 9, 9, and 7cmH(2)O for C4. C3 stimulation produced modest Pdi responses, whereas C5 stimulation could produce Pdi responses close to those observed with C4 stimulation. These singular observations confirm the dominance of C4 in diaphragm innervation but suggest than C5 can be of importance.     

Elevated circulating levels of tumor necrosis factor in severe chronic heart failure

BACKGROUND AND METHODS. Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure. RESULTS. Mean (+/- SEM) serum levels of tumor necrosis factor were higher in the patients with heart failure (115 +/- 25 U per milliliter) than in the healthy controls (9 +/- 3 U per milliliter; P less than 0.001). Nineteen of the patients with chronic heart failure had serum levels of tumor necrosis factor greater than or equal to 39 U per milliliter (greater than 2 SD above the mean value for the control group), whereas the remaining 14 patients had serum levels of tumor necrosis factor below this level. The patients with high levels of tumor necrosis factor were more cachectic than those with low levels (82 +/- 3 vs. 95 +/- 6 percent of ideal body weight, respectively; P less than 0.05) and had more advanced heart failure, as evidenced by their higher values for plasma renin activity (2.92 +/- 0.53 vs. 1.06 +/- 0.53 ng per liter per second [10.5 +/- 1.9 vs. 3.8 +/- 1.9 ng per milliliter per hour]; P less than 0.01) and lower serum sodium concentration (135 +/- 1 vs. 138 +/- 1 mmol per liter; P less than 0.05). The group with high levels of tumor necrosis factor also had lower hemoglobin levels (7.82 +/- 0.2 vs. 8.69 +/- 0.4 mmol per liter [12.6 +/- 0.4 vs. 14.0 +/- 0.6 g per deciliter]) and higher values for blood urea nitrogen (19.5 +/- 2.2 vs. 12.5 +/- 1.8 mmol per liter) than the group with low levels of tumor necrosis factor (P less than 0.05 for both). The high levels of tumor necrosis factor were not due solely to decreased renal clearance, however, since the levels in the patients with heart failure were considerably higher than those in the nine patients with chronic renal failure (115 +/- 25 vs. 45 +/- 25 U per milliliter; P less than 0.05). CONCLUSIONS. These findings indicate that circulating levels of tumor necrosis factor are increased in cachectic patients with chronic heart failure and that this elevation is associated with the marked activation of the renin-angiotensin system seen in patients with end-stage cardiac disease.     

Characteristics of diaphragmatic fatigue during exhaustive exercise until task failure

The diaphragm was postulated to fatigue relatively early during exhaustive whole body exercise without further loss in contractility as exercise proceeds towards task failure. Diaphragmatic contractility was investigated prior/during/after exhaustive whole body exercise until task failure by using lung volume corrected twitch transdiaphragmatic pressure (TwPdi(c)) during magnetic phrenic nerve stimulation (every 45s). Eleven cyclists exercised to exhaustion (workloads ≥85% maximal oxygen uptake; 20.7±9.8min). Individual post hoc calculation of TwPdi(c) was conducted (diaphragmatic contractility versus lung volume). Diaphragmatic fatigue (i.e. TwPdi reduction baseline/recovery ≥10%) occurred in 9/11 subjects (82% "fatiguers"; baseline/recovery TwPdi(c) -16±13%, p<0.01). Fatiguers TwPdi(c) was: baseline: 2.99±0.40kPa, exercise-onset: 2.98±0.41kPa, initial third: 2.80±0.67kPa, second third: 2.54±0.55kPa, final third-task failure: 2.51±0.44kPa, recovery: 2.50±0.52kPa. Diaphragmatic contractility and lung volume (rest) were strongly related (r(2)=0.98, mean TwPdi(c) gradient 0.78kPa/l). To conclude, diaphragmatic contractility (lung volume corrected) decreases relatively early (initial two thirds) during exhaustive exercise and remains preserved towards task failure. This confirms previous assumptions postulating that respiratory performance is sustained without further fatigue of the primary inspiratory muscle.     

Respiratory response to mechanical stimulation of the gallbladder

Since stimuli from abdominal or pelvic viscera can affect respiratory muscle function, we hypothesized that mechanical stimulation of the gallbladder would result in inhibition of motor activity to the diaphragm and to upper airway muscles. We studied 12 decerebrate, vagotomized, paralyzed, artificially ventilated cats and recorded hypoglossal (HG) and phrenic (PHR) nerve activities while applying 600-1000 g of traction on the gallbladder during four respiratory cycles. Traction resulted in an initial reduction of PHR activity to 87.6+/-15.0% (mean+/-S.D.% of its baseline value), a reduction of HG activity to 74.2+/-27.5% and a lengthening of expiratory time to 178.8+/-81.0%. Subsequently, PHR activity and expiratory time returned toward control values, while HG remained diminished, at 66.4+/-19.1%. Our results show that mechanical stimulation of the gallbladder results in a respiratory inhibition with a disproportionate reduction in HG activity relative to PHR discharge. We speculate that gallbladder stimulation by contractions or surgery may compromise breathing by inhibition of phrenic discharge and upper airway obstruction.     

Treatment of symptomatic hyponatremia and its relation to brain damage. A prospective study

We studied the effects of replacement therapy in two groups of patients with symptomatic hyponatremia. Thirty-three patients, who were studied prospectively, had no evidence of cerebral demyelinating lesions. Their hyponatremia (mean serum sodium concentration [+/- SE], 108 +/- 1 mmol per liter) was increased to 126 +/- 1 mmol per liter with hypertonic saline (856 mM) delivered at a rate of 1.3 +/- 0.2 mmol per liter per hour. The serum sodium concentration did not rise to normal or hypernatremic levels in the first 48 hours of therapy, and none of these patients had a respiratory arrest or other hypoxic episode. Twelve patients, evaluated retrospectively, had evidence of cerebral demyelinating lesions at autopsy or on computerized axial tomography. The rate of correction of hyponatremia (1 +/- 0.2 mmol per liter per hour) was similar to the rate in the patients in Group I. However, at least one of four characteristics was present: an increase in serum sodium to normal or hypernatremic levels in the first 48 hours, a change in the serum sodium concentration of more than 25 mmol per liter in the first 48 hours, a hypoxic-anoxic episode, and an elevation of serum sodium to hypernatremic levels in patients with hepatic encephalopathy. Although these four features were associated with demyelination, our observations suggest that this complication does not depend on the rate of correction of hyponatremia.     

Phosphatemic control during acute renal failure: intermittent hemodialysis versus continuous hemodiafiltration

BACKGROUND: Achieving "adequacy of dialysis" includes the maintenance of normal serum phosphate concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. METHODS: We compared the effects of continuous veno-venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum phosphate concentrations using daily morning blood tests in 88 consecutive intensive care patients half of which were treated with IHD and half with CRRT RESULTS: Mean patient age was 54+/-14 years for IHD and 60+/-14 years for CVVHDF (NS). However, patients who received CVVHDF were more critically ill (mean APACHE II scores: 24.4+/-5.1 for IHD vs. 29.2+/-5.7 for CVVHDF, p<0.003). Before treatment, the serum phosphate concentration was 2.04+/-0.16 mmoll L for IHD and 1.96+/-0.17 mmoll L for CVVHDF (NS), with abnormal values in 79.4% of IHD patients and in 64.8% of CVVHDF patients (NS). During treatment, CVVHDF induced a greater reduction in serum phosphate (p=0.02) during the first 48 hours and conferred superior subsequent control of hyperphosphatemia (achieved in 64.6% of observations during CVVHDF vs. 41.8% during IHD; p<0.0001). The serum phosphate concentration was also more likely to be within the normal range during CVVHDF (55.3% vs.36.2%; p<0.0001). There was a trend toward more frequent hypophosphatemia (9.3% vs. 5.6%; P<0.1) during CVVHDF CONCLUSIONS: Abnormal serum phosphate concentrations are frequent in ARF patients before and during renal replacement, however, normalization of phosphatemia is achieved more frequently with CVVHDF.     

Effects of acute hypercalcaemia on blood pressure in subjects with and without parathyroid hormone secretion

AIM: Acute hypercalcaemia increases the blood pressure, but the mechanism is uncertain. It may partly be the result of the concomitant fall in parathyroid hormone (PTH) secretion as PTH has been reported to have a vasodilator effect. To elucidate this, we infused calcium intravenously in subjects with and without PTH secretion. METHODS: Seven thyroparathyroidectomized subjects with undetectable PTH levels and 10 controls were studied twice, once with a calcium clamp technique that increased plasma ionized calcium in two steps of 0.1 mmol L(-1), each step lasting 60 min, and once with a placebo infusion. RESULTS: On the placebo day, blood pressure and all other variables were unaffected in both groups. On the calcium day, systolic blood pressure increased gradually and significantly from end of baseline till end of the calcium infusion in the controls (123.5 +/- 19.8 and 134.2 +/- 17.6 mmHg, P < 0.004) but not in the thyroparathyroidectomized subjects (124.9 +/- 15.7 and 126.0 +/- 20.6 mmHg, P = ns). Serum PTH levels fell promptly in the controls, and in both groups there was a significant increase in serum phosphate. The diastolic blood pressure and pulse rate, and the plasma adrenaline and noradrenaline, plasma renin activity, and serum aldosterone levels were unaffected by the calcium infusion. CONCLUSION: During acute hypercalcaemia the blood pressure increase appears unrelated to catecholamine secretion and the renin-aldosterone system, whereas the fall in PTH secretion may play a contributory role.     

Effects of a three-hour calcium clamp on calcium, phosphate, magnesium and zinc concentrations of human parotid saliva

Ionized (saliva-Ca2+) and total calcium (saliva-CaT), inorganic phosphate (saliva-P), magnesium (saliva-Mg), and zinc (saliva-Zn) levels in parotid saliva were studied in eight healthy volunteers during a 3-h calcium infusion, directly regulated to obtain a pre-settled standardized blood calcium level. Frequent determinations of whole blood ionized calcium (B-Ca2+) were used for continuous adjustments of the calcium infusion rate ('calcium clamp'). Basal B-Ca2+ (1.26 +/- 0.04 mmol X l-1, mean +/- SD) was thus elevated to and maintained at 1.51 +/- 0.05 mmol X l-1 from +30 to +180 min. Saliva samples were taken prior to the infusion and at regular intervals during the infusion period. Saliva-Ca2+ decreased from 0.38 +/- 0.06 to 0.33 +/- 0.05 mmol X l-1 (P less than 0.01) and saliva-Ca2+ as a percentage of saliva CaT from 63 +/- 7% to 53 +/- 10% (P less than 0.001) during the infusion. No changes could be observed in saliva-CaT, saliva-P, saliva-Mg, saliva-Zn, saliva-Na and saliva-K. Possible mechanisms behind these findings might be decreased parathyroid hormone and increased calcitonin concentrations in serum.     

The acidosis of cholera. Contributions of hyperproteinemia, lactic acidemia, and hyperphosphatemia to an increased serum anion gap

To study the metabolic acidosis that occurs during the diarrhea of cholera, we examined the serum anion gap in 21 patients with hypovolemic shock due to Vibrio cholerae infection. Measurements of serum electrolytes, as well as divalent cations and the anionic contributions of serum proteins, lactate, phosphate, and serum creatinine, were made at the time of admission, after rehydration, and during convalescence. At the time of admission, the mean serum concentration of sodium was 134.8 mmol (meq) per liter, that of chloride was 103.2 mmol per liter, and that of bicarbonate was 11.4 mmol per liter; the mean anion gap was 20.2 mmol per liter. The mean serum creatinine concentration was 2.48 mg per deciliter. The low serum bicarbonate level and the high serum anion gap were corrected by rehydration. The increased serum anion gap was caused by hyperproteinemia, lactic acidemia, and hyperphosphatemia, with anionic contributions to the rise in anion gap estimated as protein, 5.5 meq per liter; lactate, 2.5 meq per liter; and phosphate, 2.5 meq per liter. The hyperproteinemia was attributed to dehydration, the lactic acidemia to shock, and the hyperphosphatemia to acidosis and transient renal failure. The mean concentrations of serum calcium and magnesium were slightly elevated but did not affect the increased anion gap. These results indicate that severe cholera causes acidosis with relatively little change in serum chloride but an increased serum anion gap. The acidosis is more profound than would be expected on the basis of stool losses of bicarbonate, because of superimposed lactic acidemia and renal failure.