The effect of septic shock on skeletal muscle action potentials in the primate.

Techniques developed for the in vivo study of cellular physiology have been applied to septic shock in primates. Measurements of skeletal muscle transmembrane resting and action potentials were correlated with an analysis of fluid and electrolyte changes in the intracellular and extracellular compartments of skeletal muscle. The data obtained indicated a marked depletion of muscle extracellular water and an increase in intracellular sodium chloride and water content during shock. The significant decrease of resting membrane potential was associated with a decrease in amplitude of the action potential and prolongation of both the repolarization and depolarization time. In addition, there was a decrease of muscle intracellular potassium concentration during shock. This study demonstrates that the alterations in cellular membranes in hemorrhagic shock and septic shock are similar.     

Effects of pH on potassium: new explanations for old observations

Maintenance of extracellular K(+) concentration within a narrow range is vital for numerous cell functions, particularly electrical excitability of heart and muscle. Potassium homeostasis during intermittent ingestion of K(+) involves rapid redistribution of K(+) into the intracellular space to minimize increases in extracellular K(+) concentration, and ultimate elimination of the K(+) load by renal excretion. Recent years have seen great progress in identifying the transporters and channels involved in renal and extrarenal K(+) homeostasis. Here we apply these advances in molecular physiology to understand how acid-base disturbances affect serum potassium.     

Potassium and intracellular pH.

Recent work has clarified some of the complex interrelationships between cell pH and potassium. These studies have been limited by the techniques available for accurately measuring cell pH. At present it is obvious that intracellular pH is a major regulator of the cellular potassium concentration, but the precise relationship between these two is still uncertain. It has become increasingly clear, however, that no simple relationship exists between the intracellular to extracellular hydrogen ion and potassium ion ratios. Many experiments do demonstrate that the extracellular metabolic alkalosis of potassium depletion is accompanied by a decrease in skeletal muscle pH in rat, rabbit, and probably dog. The response of cardiac and renal tubular cell pH to potassium depletion is less clear, although most evidence indicates that there is also a reduction in the pH of these tissues. This effect on cell pH appears to be independent of chloride. By contrast, hyperkalemia seems to raise muscle cell pH at the same time it induces an extracellular metabolic acidosis. The metabolic and physiologic consequences of potassium-induced alterations in cell pH have yet to be fully elucidated.     

Biochemical changes associated with the use of haemodilution with 5% dextrose in water and mannitol for open-heart surgery

Many advantages are gained from the use of haemodilution in open-heart surgery. There is a lessened post-operative morbidity from bleeding, renal failure, and serum hepatitis. However, dilution with 5% dextrose in water is associated with a greater metabolic acidosis and a higher incidence of serious dysrhythmias than is pure blood. In order to elucidate the causes of these complications, 26 patients were studied using different degrees of haemodilution. The metabolic acidosis appeared to be mainly due to the dilution of blood buffer. Changes in electrolyte balance were more marked with greater dilution. The effects on serum sodium and chlorides were transient. The serum potassium level fell markedly during the post-operative phase and was associated with dysrhythmias. We believe that variation in potassium concentration is due to redistribution of potassium between the intracellular and extracellular phase as well as to an increased urinary excretion of potassium. The acidosis and hypokalaemia can be rapidly corrected by the administration of sodium bicarbonate and potassium. The changes in acid-base metabolism and electrolyte balance can possibly be prevented by suitably modifying the priming fluid.     

Acute renal failure in a burn patient: the advantages of continuous peritoneal dialysis

An 8-year-old girl sustained 65–70 per cent body surface area burns when her clothes caught fire. Two weeks later, she developed acute renal failure (ARF) and needed dialysis therapy. The extensive, infected burn area prevented the establishment of a safe vascular access for haemodialysis. Continuous peritoneal dialysis proved to be a valid alternative form of treatment and even had advantages over haemodialysis. Large amounts of fluids, calories and electrolytes could be administered via the peritoneal route. This facilitated the treatment of the catabolic state of the uraemic burn patient and served to correct the electrolyte losses via the skin. Peritoneal dialysis is a valuable adjunct to the treatment of acute renal failure in burn patients who need renal replacement therapy.     

The management of white phosphorus burns.

Phosphorus burns are a rarely encountered chemical burn, typically occurring in battle, industrial accidents, or from fireworks. Death may result even with minimal burn areas. Early recognition of affected areas and adequate resuscitation is crucial. Amongst our 2765 admissions between 1984 and 1998, 326 patients had chemical burns. Seven admissions were the result of phosphorus burns. Our treatment protocol comprises 1% copper sulfate solution for neutralization and identification of phosphorus particles, copious normal saline irrigation, keeping wounds moist with saline-soaked thick pads even during transportation, prompt debridement of affected areas, porcine skin coverage or skin grafts for acute wound management, as well as intensive monitoring of electrolytes and cardiac function in our burns center. Intravenous calcium gluconate is mandatory for correction of hypocalcemia. Of the seven, one patient died from inhalation injury and the others were scheduled for sequential surgical procedures for functional and cosmetic recovery. Cooling affected areas with tap water or normal saline, prompt removal of phosphorus particles with mechanical debridement, intensive monitoring, and maintenance of electrolyte balance are critical steps in initial management. Fluid resuscitation can be adjusted according to urine output. Early excision and skin autografts summarize our phosphorus burn treatment protocol.     

Studies on the energy expenditure following surgical stress (I. The effects of the severity of stress and the administration of nutrients)

Energy expenditure was studied in male Donryu rats, following two types of surgical stress, namely, laparotomy and burns. The rats with burns were subsequently fasted for 6 hours, by which time the resting metabolic expenditure (RME) became significantly decreased (84.3±9.5 per cent), as when compared to the pre-burn value (100 per cent), then increased 24 hours after the burn (132.9±10.1 per cent). The RME in burned rats receiving an intravenous infusion of electrolyte fluid, slightly increased 6 hours after the burn (109.0±15.8 per cent) and was almost identical to the RME in rats fedad libitum for 24 hours after the burn. Rats with burns, that were given intravenous infusions of electrolytes and nutrients (TPN) already had a high RME value (134.6±7.0 per cent) 6 hours after the burn. In laparotomized rats fedad libitum, no obvious changes in energy expenditure were observed 6 hours or 24 hours after the laparotomy, however, rats receiving TPN showed a moderately increased RME 6 hours after the laparotomy (113.9±3.4 per cent, p<0.05) which returned to the pre-stress level 24 hours post-operatively. These results confirmed that a phase of decreased RME (ebb phase), followed by a phase of increased RME were clearly observed after severe surgical stress, which indicated that appropriate treatments could shorten or extinguish the ebb phase.     

Muscle chemistry of critically ill surgical patients and the effects of a course of intravenous nutrition.

The water, electrolyte and nitrogen contents of muscle were measured in 15 critically ill surgical patients before and after a course (approximately 2 weeks) of intravenous nutrition and in 8 normal individuals. The muscle from the surgical patients contained a significantly increased ratio of water to fat-free dry weight (P less than 0.01) due to an increase in the proportion of extracellular to intracellular water, and this was not corrected by intravenous nutrition. These changes could be due to an accumulation of extracellular fluid alone or to a loss of cell cytoplasm or a loss of whole muscle fibres. Intracellular chemistry was normal in the ill surgical patients and was not changed by intravenous nutrition.     

The effects of resuscitation with hypertonic vs. hypotonic vs. colloid on wound and urine fluid and electrolyte losses in severely burned children

Thirty-nine children with large burns were resuscitated with either a hypertonic (HLS) (17 patients), hypotonic (11 patients), or colloid (11 patients) fluid regimen. Burn dressings, bed linen, and urine were analyzed for electrolyte content. The group receiving HLS excreted the greatest percentage of the administered sodium load in the urine, significantly more than the other two groups; however, the combined wound and urinary sodium losses were significantly greater for the group receiving colloid. Sodium loss through the burn wound exceeded urinary loss fivefold in the colloid group. The volume of fluid lost across the burn wound was inversely related to the osmolality of the fluid used for resuscitation. Wound sodium loss was a function of both sodium and fluid load. The flux of fluid and electrolytes across the burn wound is a dynamic part of the resuscitation problem and is dramatically effected by the volume and concentration of fluid used.     

Influence of injury and nutrition on muscle water and electrolytes: effect of severe injury, burns and sepsis

The changes in water and electrolyte metabolism associated with severe injury and sepsis are well recognized but changes in tissue content have seldom been available. This report combines the experience obtained from muscle biopsies of such patients performed in two centers; one located in Sweden and one in the U.S. Normal values for muscle water and electrolytes in each center are in close agreement. Needle biopsies of muscle were performed in 45 Swedish patients and 17 U.S. patients at intervals after injury or infection from the second to the thirtieth day. The patients' nutrition varied from brief periods of hypocaloric intake to prolonged high calorie parenteral nutrition with and without amino acids, as well as with and without fat. Prominent changes appeared during the first week and persisted up to 30 days regardless of the associated nutritional intake. These changes included an increased total muscle water, extracellular water, sodium and chloride and a decrease in muscle potassium and magnesium. This study demonstrates a simultaneous expansion of extracellular volume and a loss of intracellular components. This is in contrast to the experiences reported with less severe injury such as elective operation, where a more modest expansion of extracellular volume is seen and which is not associated with any loss of potassium or magnesium. The magnitude and persistence of these changes in muscle tissue deserve further study, both as to mechanism and implications for therapy.     

Uremic acidosis and intracellular buffering

Skeletal muscle biopsies were performed in 16 controls and 15 non-dialysed end-stage chronic renal failure (CRF) patients presenting untreated metabolic acidosis. Intracellular bicarbonate, pH, water compartments and electrolytes were determined. In 8 of 15 patients muscle ATP and lactate were measured. Intracellular bicarbonate (HCO3i) and pH (pHi) were obtained by means of muscle total carbon dioxide method: a significant (p less than 0.001) reduction in both intracellular acid--base indexes was found in all patients (pHi 6.82 +/- 13 vs. 7.04 +/- 0.05; HCO3i 6.28 +/- 2.07 vs. 11.86 +/- 0.87). Total muscle as well as extracellular water was increased. Muscle sodium and chloride contents were also increased, while no change in potassium and magnesium was detected. A significant decrease of both muscle ATP and lactate was found. The data lead to the conclusion that chronic retention of acids in CRF results in a depletion of the muscle buffer pool and consequently in intracellular acidosis: the latter could be the main cause of the cell energy metabolism derangement described in uremia.     

Recent concepts regarding the resuscitation of the burned patient

THERE is considerable discussion regarding immediate plasma, electrolytes and fluid replacement in the acute phase after burns. Intravenous input of saline was begun by Reiss in 1880, and later in 1897 was advocated by Tommasoli (Hauben et al., 1981), when hypovolaemic shock and its sequelae were under study. Plasma, electrolytes and fluids have been established as routine formulae (e.g. Evans, Brooke, Parkland and Odstock formulae), differing from each other in their various constituents. The aim of this paper is to present the four main contemporary concepts regarding the efficient and ideal treatment to be given during the shock period in the acute phase after burns, as expressed by four teams treating burns in their acute and critical phase.     

Bicarbonate buffered ultrafiltration leads to a physiologic priming solution in pediatric cardiac surgery

Pediatric cardiopulmonary bypass (CPB) involves a high ratio of priming blood volume to patient blood volume. The composition of packed red blood cells (RBCs) is very unphysiological in terms of acid-base, electrolyte and metabolite values. Therefore, we tested the hypothesis whether ultrafiltration of the prime and replacement with bicarbonate buffered hemofiltration solution (BB-HS) is sufficient for reducing the metabolic load and reaching a physiologic state. For planned surgery of congenital heart defects with cardiopulmonary bypass, 20 CPB circuits were primed with BB-HS, gelatin and 1 unit of RBCs. The fluid was hemofiltrated using an ultrahemofilter at 300 ml/min until approximately 1000 ml of ultrafiltrate was restored with BB-HS. Blood gas analyses were obtained from the priming blood, once before and once after bicarbonate buffered ultrafiltration (BBUF). The measured substrates decreased significantly (P<0.001) after BBUF (glucose from 13.0+/-2.6 to 6.3+/-1.0 and lactate from 3.8+/-1.5 to 2.3+/-1.0 mmol/l). Acid-base parameters increased (P<0.001) to normal or high normal values (pH from 7.01+/-0.09 to 7.68+/-0.12; HCO(3) from 12.1+/-2.4 to 25.4+/-3.6 mmol/l and BE from -15.4+/-3.6 to -0.8+/-3.7 mmol/l). Even the electrolytes sodium, potassium and calcium changed significantly (P<0.001) toward the physiologic range. BBUF is an efficient method of reducing the metabolic load of priming. After BBUF, even the electrolyte and acid-base balance reached a physiologic state, which is important for minimizing electrolyte and acid-base disturbances after initiation of CPB.     

Acute infusion of amphotericin B: Proximal tubular effects

Summary: Electron microprobe analysis (EMPX) was employed to determine the alterations in intracellular electrolyte concentrations in proximal tubular cells resulting from acute treatment with amphotericin B. Concurrent clearance data confirmed a drop in glomerular filtration rate (GFR) in the rats treated with amphotericin B infusion (1 mg/kg per h) compared to control animals infused with saline (0.69 ± 0.11 vs 1.27 ± 0.08 mL/min per 100 g; P < 0.001). Measurement of intracellular electrolytes in proximal tubular cells in mmol/kg wet weight by EMPX demonstrated no difference in Na (16.2 ± 0.6 vs 17.2 ± 0.5) or K (129.7 ± 2.1 vs 131.3 ± 2.0). Intracellular Rb accumulation following acute infusion was significantly reduced in the amphotericin B treated animals (3.9 ± 0.4 vs 6.6 ± 0.4; P < 0.0001), suggestive of a reduction in basolateral Na-K ATPase activity. These results do not support the tenet that amphotericin B causes a generalized increase in epithelial cell membrane ionic permeability, nor direct tubular toxicity in the doses and time frame studied. Rather, they suggest that a primary reduction in GFR results acutely in a load-dependent decrease in proximal tubular Na transport.     

The relationship between disorders of K+ and Mg+ homeostasis

Potassium and magnesium balance are frequently altered by common pathological conditions. Isolated disturbances of potassium balance do not produce secondary abnormalities in magnesium homeostasis. In contrast, primary disturbances in magnesium balance, particularly magnesium depletion, produce secondary potassium depletion. This appears to result from an inability of the cell to maintain the normally high intracellular concentration of potassium, perhaps as a result of an increase in membrane permeability to potassium and/or inhibition of Na+-K-ATPase. As a result, the cells lose potassium, which is excreted in the urine. Repletion of cell potassium requires correction of the magnesium deficit. Are such magnesium dependent alterations in potassium balance of any clinical significance? Within the context of electrolyte disturbances, magnesium replacement is often necessary before hypokalemia and potassium depletion can be satisfactorily corrected with potassium supplements. The hyponatremia often seen with chronic diuretic usage may also be related to depleted intracellular potassium stores. In a small group of patients with chronic congestive heart failure, magnesium replacement alone was sufficient to correct this hyponatremia. Finally, magnesium and potassium depletion may play an important role in the development of cardiac arrhythmias in certain select groups of patients, such as those with overt ischemic heart disease. The frequency of magnesium depletion in some clinical disease states warrants renewed interest in the relationship between magnesium and potassium homeostasis.     

Acetate-Free Biofiltration in Acute Renal Failure

Abstract: Hemodialysis treatment for acute renal failure is associated with a high incidence of adverse reactions. Hemodynamic stability and adequate correction of acid-base and hydroelectrolyte imbalance are the main goals of dialytic strategy in acute renal failure. However, the variety of etiology and the diversity of clinical conditions suggest that individualized treatment may be advisable. To this purpose, in 26 patients suffering from "isolated" acute renal failure of different etiologies, we have used acetate-free biofiltration. We have performed 411 dialyses with an extremely low incidence of symptomatic treatments and remarkable cardiovascular stability. Correction of fluid, electrolyte, and acid-base imbalance proved excellent. Dialytic efficacy proved adequate. Our data show that acetate-free biofiltration is an easy technique suitable for individualized treatment and adaptable to changing needs during hemodialysis in patients with isolated acute renal failure.     

Potassium homeostasis and its disturbances in children

Although only 2% of the body potassium is present in the extracellular space, its concentration is finely regulated by the internal balance, or distribution of potassium between the intracellular and extracellular compartments, and by the external balance, or difference between intake and output of potassium. Internal balance is modulated by a host of factors, including insulin, epinephrine, extracellular pH and plasma tonicity. Potassium output from the body is mainly determined by renal excretion. Renal secretion of potassium takes place predominantly in the principal cells of late distal and cortical collecting tubules, by a process involving the accumulation of potassium in the cell by the activity of the basolateral Na⁺,K⁺-ATPase and its exit through luminal conductive channels. The factors regulating renal potassium secretion are potassium intake, rate of tubular fluid flow, distal sodium delivery, acid-base status and aldosterone. Hypokalaemia may result from a low potassium intake, excessive gastrointestinal, cutaneous or renal losses and altered body distribution. Aetiological diagnosis and therapy are best accomplished when the acid-base status is assessed at the same time. Before establishing the diagnosis of hyperkalaemia, spurious hyperkalaemia due to haemolysis or release of potassium from cells during clot retraction (pseudohyperkalaemia) should be ruled out. Hyperkalaemia may result from exogenous or endogenous loading, decreased renal output and altered body distribution. Acute hyperkalaemia represents an emergency situation which requires immediate therapy.     

The effect of parenteral nutritional repletion on muscle water and electrolytes. Implications for body composition

Nutritional depletion and repletion are associated with changes in the size of the extracellular and intracellular fluid compartments. Although the effect of nutrition on whole body composition is well established, the distribution of changes among the various body tissues is not. This study correlates changes in skeletal muscle composition with whole body electrolyte and nitrogen balance in an attempt to establish the contribution made by skeletal muscle to the changes in whole body fluid and electrolyte composition. Total parenteral nutrition was administered to ten patients for 16 to 25 days. Oxygen consumption, CO2 production, and balances of N, Na, and K were measured daily. Muscle biopsies were taken prior to administration of TPN, in the middle, and at the end of the nutritional regimen. Prior to administration of parenteral nutrition, muscle concentrations of water, sodium, and chloride were significantly higher than normal. With institution of the nutritional support regimen, all three concentrations decreased. The calculated loss in muscle water could account, at most, for only one-sixth of the loss in total body water. Muscle Na loss could account for approximately one-half of the whole body change. Potassium concentrations in the depleted patients were not significantly decreased from normal values and showed a negligible increase with TPN. Since the ratio of K to dry fat-free solids in muscle was constant, most of the whole body changes could be accounted for by assuming that nearly all N is deposited in muscle. Nutritional support results in restoration of cell mass with a contraction of the extracellular fluid (ECF) compartment. The changes in the ECF must occur in tissues other than muscle, while the restoration of cell mass occurs primarily in muscle.     

Hepatocyte dysfunction in thermal injury

Transmembrane potential difference (PD) is a reliable indicator of cellular function. Decreased PD in hepatocytes in hemorrhagic shock occurred concomitant with decreased adenosine triphosphate (ATP), suggesting energy depletion as the mechanism of cell dysfunction. This study correlates changes in liver and muscle PD with hepatocyte ATP, glucose-6-phosphate (G-6-P), and lactate levels in burn shock and resuscitation. Six adult female baboons were subjected to 52.4 +/- 6.3% body surface area third-degree scald burns. The animals were resuscitated using the Parkland formula, after the muscle PD had fallen to -70 mV. Liver PD decreased from 46.2 +/- 2.4 mV to 22.4 +/- 3.8 mV in burn shock. The PD recovered toward normal with resuscitation. ATP and G-6-P contents did not change significantly, while lactate rose threefold in burn shock. A severe cellular derangement was indicated by this marked hepatocyte depolarization. Maintenance of normal intracellular ATP excludes energy depletion as the mechanism of this cell dysfunction. These findings are consistent with failure of active ion transport or changes in cell membrane permeability which were partially recovered during fluid resuscitation.     

The influence and effectiveness of hydrochloric acid infusion on the extra- and intracellular acid-base status in vivo. Experimental study on rat tissue

The influence of HCl infusion on extra- and intracellular acid-base status of liver, brain, heart, and skeletal muscle of nephrectomized rats was investigated in vivo. The present results showed that a decrease of extracellular plasma pH was followed by similar changes of the intracellular pH of the investigated tissues and a loss of bicarbonate from extracellular and intracellular body compartment. The results lead to the conclusion that HCl seems to be a suitable agent for correction of severe metabolic alkalosis.