Effects of antihypertensive drugs on blood pressure and proteinuria in childhood

BACKGROUND: Historically, there have been few drug trials for antihypertensive treatment in childhood and recommendations have been extrapolated from data obtained in adulthood. During the last decade an increased awareness of the risks of childhood hypertension stimulated clinical trials of antihypertensive agents in children. OBJECTIVE: The aim of this article is to systematically review the studies published between 1995 and 2006 that deal with the effect of antihypertensive drugs on childhood hypertension or proteinuria. METHODS: Medline, Current Contents, personal files and reference lists were used as data sources. RESULTS: Fifty-two out of 79 initially found reports were excluded. Consequently 27 articles were retained for the final analysis. The blood pressure reduction was similar with angiotensin-converting enzyme inhibitors (10.7/8.1 mmHg), angiotensin II receptor antagonists (10.5/6.9 mmHg) and calcium-channel blockers (9.3/7.2 mmHg). In addition angiotensin-converting enzyme inhibitors (by 49%) and angiotensin II receptor antagonists (by 59%) significantly reduced pathological proteinuria. CONCLUSIONS: The blood pressure reduction of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and calcium-channel blockers is almost identical. In children with pathological proteinuria angiotensin-converting enzyme inhibitors or angiotensin II antagonists are superior to calcium-channel blockers.

Novel pressure-to-cornea index in glaucoma

BACKGROUND: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures <or=21 mm Hg, 140 when untreated pressure >or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.

[Fixed-combination of losartan/hydrochlorothiazide 100 mg/25 mg. Tolerability and efficacy on blood pressure measured in the practice and for 24 hours]

BACKGROUND: A high proportion of patients with essential hypertension need a combination therapy to reach the therapeutic goal. In the present study, the tolerability and efficacy of a fixed, once daily combination of the AT1 blocker Losartan (100 mg) and the diuretic hydrochlorothiazide (HCTZ) (25 mg) for patients in the real-life situation was investigated. Special consideration was given to the results of ambulatory 24-hourblood pressure (ABP) measurements. METHODS: The open label, prospective non-interventional surveillance study took place from October 2005 to June 2006. A total of 1139 patients over 18 years in age were included whose blood pressures could not be adequately treated with HCTZ alone and for whom an individual dose titration for Losartan and HCTZ had already been performed. RESULTS: The average age (+/- standard deviation) of the patients was 61.2 +/- 11.6 years; 55.8% were men. Comorbidities were common. Specifically, left ventricular hypertrophy was present in 3.1% of the patients, coronary heart disease in 30.1%, chronic heart failure in 11.8% and status post myocardial infarction in 10.5%, respectively. In addition to the Losartan/HCTZ treatment, 61.0% of the patients received a second antihypertensive medicine. After an average treatment duration of 50.4 +/- 17.2 days, the base line systolic blood pressure of 160.8 +/- 16.3 mmHg decreased by 24.0 +/- 17.0 mmHg (-14.4%) and the diastolic blood pressure of 94.4 +/- 9.9 mmHg decreased by 11.8 +/- 10.2 mmHg (-11.8%). For the ABP measurements, the overall average systolic and diastolic blood pressures fell by 16.9 +/- 14.2 mmHg and 8.8 +/-10.3 mmHg, the day average by 17.3 +/- 14.8 mmHg and 9.0 +/- 10.2 mmHg and the night average by 15.1 +/- 17.6 mmHg and 7.8 +/- 11.7 mmHg, respectively. In twelve of the 1139 patients (1.1%), a total of 15 adverse events occurred. A causal connection with the medication was suspected in only in one case (one patient with three). CONCLUSION: The combination of Losartan/HCTZ 100/25 mg, as the exclusive therapy or in addition to other antihypertensive medicines, was for patients, many of whom who had comorbidities, in the real-life situation well tolerated and effective. The efficacy was demonstrated also during the night through ABP.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure

OBJECTIVE: To compare the effect of bimatoprost and the fixed combination of latanoprost and timolol (LTFC) on 24-hour mean intraocular pressure (IOP) after patients are switched from a nonfixed combination of latanoprost and timolol. DESIGN: Randomized, double-masked, multicenter clinical trial. PARTICIPANTS: Two hundred patients with glaucoma or ocular hypertension. METHODS: Included were patients who were controlled (IOP < 21 mmHg) on the nonfixed combination of latanoprost and timolol for at least 3 months before the baseline visit or patients on monotherapy with either latanoprost or timolol who were eligible for dual therapy not being fully controlled on monotherapy. The latter group of patients underwent a 6-week wash-in phase with the nonfixed combination of latanoprost and timolol before baseline IOP determination and study inclusion. Supine and sitting position IOPs were recorded at 8 pm, midnight, 5 am, 8 am, noon, and 4 pm at baseline, week 6, and week 12 visits. MAIN OUTCOME MEASURE: An analysis of covariance model was used for a noninferiority test of the primary efficacy variable, with mean area under the 24-hour IOP curve after 12 weeks of treatment as response variable and treatment, center, and baseline IOP as factors. A secondary analysis was performed on the within-treatment change from baseline. RESULTS: Mean baseline IOPs were 16.3+/-3.3 mmHg and 15.5+/-2.9.mmHg in the bimatoprost and LTFC groups, respectively. At week 12, mean IOPs were 16.1+/-2.5 mmHg for the bimatoprost group and 16.3+/-3.7 mmHg for the LTFC group, and no significant difference between the 2 treatment groups could be found. As compared with baseline, mean IOP increased by 0.3+/-3.6 mmHg during the day and decreased by 0.8+/-3.8 mmHg during the night in the bimatoprost group, whereas there were increases of 1.43+/-2.6 mmHg and 0.14+/-3.2 mmHg in the LTFC group, respectively. CONCLUSIONS: Bimatoprost is not inferior to the LTFC in maintaining IOP at a controlled level during a 24-hour period in patients switched from the nonfixed combination of latanoprost and timolol.

The "flap-shaft" prosthesis for insensate feet with Chopart or Lisfranc amputations

BACKGROUND: The inevitable detachment of tendons and the loss of the forefoot in Chopart and Lisfranc amputations result in equinus and varus of the residual foot. In an insensate foot these deformities can lead to keratotic lesions and ulcerations. The currently available prostheses cannot safely counteract the deforming forces and the resulting complications. METHODS: A new below-knee prosthesis was developed, combining a soft socket with a rigid shaft. The mold is taken with the foot in the corrected position. After manufacturing the shaft, the lateral third of the circumference of the shaft is cut away and reattached distally with a hinge, creating a lateral flap. By closing this flap the hindfoot is gently levered from the varus position into valgus. Ten patients (seven amputations at the Chopart-level, three amputations at the Lisfranc-level) with insensate feet were fitted with this prosthesis at an average of 3 (range 1.5 to 9) months after amputation. The handling, comfort, time of daily use, mobility, correction of malposition and complications were recorded to the latest followup (average 31 months, range 24 to 37 months after amputation). RESULTS: Eight patients evaluated the handling as easy, two as difficult. No patient felt discomfort in the prosthesis. The average time of daily use was 12 hours, and all patients were able to walk. All varus deformities were corrected in the prosthesis. Sagittal alignment was kept neutral. Complications were two minor skin lesions and one small ulcer, all of which responded to conservative treatment, and one ulcer healed after debridement and lengthening of the Achilles tendon. CONCLUSIONS: The "flap-shaft" prosthesis is a valuable option for primary or secondary prosthetic fitting of Chopart-level and Lisfranc-level amputees with insensate feet and flexible equinus and varus deformity at risk for recurrent ulceration. It provided safe and sufficient correction of malpositions and enabled the patients to walk as much as their general condition permitted.

Subcutaneous oxygen pressure in spontaneously breathing lean and obese volunteers: a pilot study

BACKGROUND: Oxidative killing is the primary defense against surgical pathogens; risk of infection is inversely related to tissue oxygenation. Subcutaneous tissue oxygenation in obese patients is significantly less than in lean patients during general anesthesia. However, it remains unknown whether reduced intraoperative tissue oxygenation in obese patients results from obesity per se or from a combination of anesthesia and surgery. In a pilot study, we tested the hypothesis that tissue oxygenation is reduced in spontaneously breathing, unanesthetized obese volunteers. METHODS: Seven lean volunteers with a body mass index (BMI) of 22 +/- 2 kg/m(2) were compared to seven volunteers with a BMI of 46 +/- 4 kg/m(2). Volunteers were subjected to the following oxygen challenges: (1) room air; (2) 2 l/min oxygen via nasal prongs, (3) 6 l/min oxygen through a rebreathing face mask; (4) oxygen as needed to achieve an arterial oxygen pressure (arterial pO(2)) of 200 mmHg; and (5) oxygen as needed to achieve an arterial pO(2) of 300 mmHg. The oxygen challenges were randomized. Arterial pO(2) was measured with a continuous intraarterial blood gas analyzer (Paratrend 7); deltoid subcutaneous tissue oxygenation was measured with a polarographic microoxygen sensor (Licox). RESULTS: Subcutaneous tissue oxygenation was similar in lean and obese volunteers: (1) room air, 52 +/- 10 vs 58 +/- 8 mmHg; (2) 2 l/min, 77 +/- 25 vs 79 +/- 24 mmHg; (3) 6 l/min, 125 +/- 43 vs 121 +/- 25 mmHg; (4) arterial pO(2) = 200 mmHg, 115 +/- 42 vs 144 +/- 23 mmHg; (5) arterial pO(2) = 300 mmHg, 145 +/- 41 vs 154 +/- 32 mmHg. CONCLUSION: In this pilot study, we could not identify significant differences in deltoid subcutaneous tissue oxygen pressure between lean and morbidly obese volunteers.

Perioperative fluid management: comparison of high, medium and low fluid volume on tissue oxygen pressure in the small bowel and colon

BACKGROUND AND OBJECTIVE: Insufficient blood flow and oxygenation in the intestinal tract is associated with increased incidence of postoperative complications after bowel surgery. High fluid volume administration may prevent occult regional hypoperfusion and intestinal tissue hypoxia. We tested the hypothesis that high intraoperative fluid volume administration increases intestinal wall tissue oxygen pressure during laparotomy. METHODS: In all, 27 pigs were anaesthetized, ventilated and randomly assigned to one of the three treatment groups (n = 9 in each) receiving low (3 mL kg-1 h-1), medium (7 mL kg-1 h-1) or high (20 mL kg-1 h-1) fluid volume treatment with lactated Ringer's solution. All animals received 30% and 100% inspired oxygen in random order. Cardiac index was measured with thermodilution and tissue oxygen pressure with a micro-oximetry system in the jejunum and colon wall and subcutaneous tissue. RESULTS: Groups receiving low and medium fluid volume treatment had similar systemic haemodynamics. The high fluid volume group had significantly higher mean arterial pressure, cardiac index and subcutaneous tissue oxygenation. Tissue oxygen pressures in the jejunum and colon were comparable in all three groups. CONCLUSIONS: The three different fluid volume regimens tested did not affect tissue oxygen pressure in the jejunum and colon, suggesting efficient autoregulation of intestinal blood flow in healthy subjects undergoing uncomplicated abdominal surgery.

Brain edema and increased intracranial pressure in the pathophysiology of bacterial meningitis

A number of advances in our understanding of the pathophysiology of bacterial meningitis have been made in recent years. In vivo studies have shown that bacterial cell wall fragments and endotoxins are highly active components, independent of the presence of viable bacteria in the subarachnoid space. Their presence in the cerebrospinal fluid is associated with the induction of inflammation and with the development of brain edema and increased intracranial pressure. Antimicrobial therapy may cause an additional increase of harmful bacterial products in the cerebrospinal fluid and thereby potentiate these pathophysiological alterations. These changes may contribute to the development of brain damage during meningitis. Some promising experimental work has been directed toward counteracting the above phenomena with non-steroidal or steroidal anti-inflammatory agents as well as with monoclonal antibodies. Although considerable advances have been made, further research needs to be done in these areas to improve the prognosis of bacterial meningitis.

Influence of granulocytes on brain edema, intracranial pressure, and cerebrospinal fluid concentrations of lactate and protein in experimental meningitis

Brain water content (brain edema), intracranial pressure, and cerebrospinal fluid (CSF) concentrations of lactate and protein increased significantly during 24 h of experimental meningitis due to Streptococcus pneumoniae, but changes were similar in normal and neutropenic rabbits. In sterile meningitis induced by N-formyl-methionyl-leucyl-phenyl-alanine (fMLP), low and high doses of fMLP were equally effective in inducing CSF pleocytosis, whereas only high doses of fMLP caused brain edema. High doses of fMLP injected intracisternally during pneumococcal meningitis also increased brain water content. The fMLP did not significantly increase intracranial pressure or CSF concentrations of lactate or protein in sterile or pneumococcal meningitis, nor did it cause brain edema in neutropenic animals. Thus, granulocytes may contribute to brain edema during meningitis if adequately stimulated, but intracranial pressure and CSF protein and lactate concentrations appear independent of granulocytes. Stimulation does not appear to occur early in meningitis, when granulocytes were without effect on brain edema.

Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis

A study was made of the effects of antibiotics and corticosteroids on parameters that reflect brain dysfunction and potential neurological damage in experimental pneumococcal meningitis in rabbits. Brain water content was 398 +/- 10 g/100 g dry weight in normal rabbits and 410 +/- 11 g in rabbits after 24 hr of infection (P less than .001). Cerebrospinal fluid (CSF) lactate levels increased from 16.3 +/- 3.4 mg/dl to 69.5 +/- 28.2 mg/dl (P less than .001), and CSF pressure increased by +8.3 +/- 3.6 mm Hg (P less than .005) over the same interval. Antibiotic therapy with ampicillin sterilized CSF and normalized CSF pressure and brain water content in all animals within 24 hr, while CSF lactate levels remained elevated. Administration of methyl prednisolone, 30 mg/kg, or dexamethasone, 1 mg/kg, 15 and 22 hr after infection completely reversed the development of brain edema, but only dexamethasone also significantly reduced the increase in CSF lactate level (43.8 +/- 12.3 mg/dl) and CSF pressure (+1.8 +/- 2.7 mm Hg). Methyl prednisolone did not significantly affect pressure or lactate levels.

Norepinephrine to increase blood pressure in endotoxaemic pigs is associated with improved hepatic mitochondrial respiration

ABSTRACT: INTRODUCTION: Low blood pressure, inadequate tissue oxygen delivery and mitochondrial dysfunction have all been implicated in the development of sepsis-induced organ failure. This study evaluated the effect on liver mitochondrial function of using norepinephrine to increase blood pressure in experimental sepsis. METHODS: Thirteen anaesthetized pigs received endotoxin (Escherichia coli lipopolysaccharide B0111:B4; 0.4 mug/kg per hour) and were subsequently randomly assigned to norepinephrine treatment or placebo for 10 hours. Norepinephrine dose was adjusted at 2-hour intervals to achieve 15 mmHg increases in mean arterial blood pressure up to 95 mmHg. Systemic (thermodilution) and hepatosplanchnic (ultrasound Doppler) blood flow were measured at each step. At the end of the experiment, hepatic mitochondrial oxygen consumption (high-resolution respirometry) and citrate synthase activity (spectrophotometry) were assessed. RESULTS: Mean arterial pressure (mmHg) increased only in norepinephrine-treated animals (from 73 [median; range 69 to 81] to 63 [60 to 68] in controls [P = 0.09] and from 83 [69 to 93] to 96 [86 to 108] in norepinephrine-treated animals [P = 0.019]). Cardiac index and systemic oxygen delivery (DO2) increased in both groups, but significantly more in the norepinephrine group (P < 0.03 for both). Cardiac index (ml/min per.kg) increased from 99 (range: 72 to 112) to 117 (110 to 232) in controls (P = 0.002), and from 107 (84 to 132) to 161 (147 to 340) in norepinephrine-treated animals (P = 0.001). DO2 (ml/min per.kg) increased from 13 (range: 11 to 15) to 16 (15 to 24) in controls (P = 0.028), and from 16 (12 to 19) to 29 (25 to 52) in norepinephrine-treated animals (P = 0.018). Systemic oxygen consumption (systemic VO2) increased in both groups (P < 0.05), whereas hepatosplanchnic flows, DO2 and VO2 remained stable. The hepatic lactate extraction ratio decreased in both groups (P = 0.05). Liver mitochondria complex I-dependent and II-dependent respiratory control ratios were increased in the norepinephrine group (complex I: 3.5 [range: 2.1 to 5.7] in controls versus 5.8 [4.8 to 6.4] in norepinephrine-treated animals [P = 0.015]; complex II: 3.1 [2.3 to 3.8] in controls versus 3.7 [3.3 to 4.6] in norepinephrine-treated animals [P = 0.09]). No differences were observed in citrate synthase activity. CONCLUSION: Norepinephrine treatment during endotoxaemia does not increase hepatosplanchnic flow, oxygen delivery or consumption, and does not improve the hepatic lactate extraction ratio. However, norepinephrine increases the liver mitochondria complex I-dependent and II-dependent respiratory control ratios. This effect was probably mediated by a direct effect of norepinephrine on liver cells.

Comparative acute effects of the calcium channel blockers tiapamil, nisoldipine, and nifedipine on blood pressure and some regulatory factors in normal and hypertensive subjects

To clarify the pharmacological profile of the two new calcium channel blockers tiapamil and nisoldipine in humans, their acute effects as compared with those of the reference agent nifedipine were assessed in 10 normal subjects and 10 patients with essential hypertension. Blood pressure (BP), heart rate (HR), plasma and urinary catecholamine, sodium and potassium, plasma renin and aldosterone levels, and urinary prostaglandin E2 and F2 excretion rates were determined before and up to 4 or 5 h (urine values) after intravenous injection of placebo (20 ml 0.9% NaCl), tiapamil 1 mg/kg body weight, nisoldipine 6 micrograms/kg, or nifedipine 15 micrograms/kg. The four studies were performed at weekly intervals according to Latin square design. All three calcium channel blockers significantly (p less than 0.05 or lower) lowered BP and distinctly increased sodium excretion in hypertensive patients, but had only little influence on these parameters in normal subjects. HR was increased in both groups. Changes in BP and HR were maximal at 5 min and largely dissipated 3 h after drug injection. Effects on BP and HR, as well as concomitant mild increases in plasma norepinephrine and renin levels that occurred in both groups, tended to be more pronounced (about double) following nisoldipine than following tiapamil or nifedipine at the dosages given. Plasma aldosterone, epinephrine levels, and prostaglandin excretion rates were not consistently modified. These findings demonstrate that tiapamil and nisoldipine possess distinct antihypertensive properties in humans. Different chronotropic and renin-activating effects of different calcium channel blockers may be determined, at least in part, by a different influence on sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen, lactate and glucose in patients with severe head injury

OBJECTIVE: The purpose of the study was to measure the effects of increased inspired oxygen on patients suffering severe head injury and consequent influences on the correlations between CPP and brain tissue oxygen (PtiO2) and the effects on brain microdialysate glucose and lactate. METHODS: In a prospective, observational study 20 patients suffering severe head injury (GCS< or =8) were studied between January 2000 and December 2001. Each patient received an intraparenchymal ICP device and an oxygen sensor and, in 17 patients brain microdialysis was performed at the cortical-subcortical junction. A 6 h 100% oxygen challenge (F IO2 1.0) ( Period A) was performed as early as possible in the first 24 hours after injury and compared with a similar 6 hour period following the challenge ( Period B). Statistics were performed using the linear correlation analysis, one sample t-test, as well as the Lorentzian peak correlation analysis. RESULTS: F IO2 was positively correlated with PtiO2 (p < 0.0001) over the whole study period. PtiO2 was significantly higher (p < 0.001) during Period A compared to Period B. CPP was positively correlated with PtiO2 (p < 0.001) during the whole study. PtiO2 peaked at a CPP value of 78 mmHg performing a Lorentzian peak correlation analysis of all patients over the whole study. During Period A the brain microdialysate lactate was significantly lower (p = 0.015) compared with Period B. However the brain microdialysate glucose remained unchanged. CONCLUSION: PtiO2 is significantly positively correlated with F IO2, meaning that PtiO2 can be improved by the simple manipulation of increasing F IO2 and ABGAO2. PtiO2 is positively correlated with CPP, peaking at a CPP value of 78 mmHg. Brain microdialysate lactate can be lowered by increasing PtiO2 values, as observed during the oxygen challenge, whereas microdialysate glucose is unchanged during this procedure. Extension of the oxygen challenge time and measurement of the intermediate energy metabolite pyruvate may clarify the metabolic effects of the intervention. Prospective comparative studies, including analysis of outcome on a larger multicenter basis, are necessary to assess the long term clinical benefits of this procedure.

High level of extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

OBJECT: Disturbed ionic and neurotransmitter homeostasis are now recognized as probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brain injury (TBI). Evidence obtained in animal models indicates that posttraumatic neuronal excitation by excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with measurements of intracranial pressure (ICP), patient outcome, and levels of dialysate glutamate and lactate, and cerebral blood flow (CBF) to determine the role of ischemia in this posttraumatic ion dysfunction. METHODS: Eighty-five patients with severe TBI (Glasgow Coma Scale Score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed using flame photometry, and dialysate glutamate and dialysate lactate levels were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients, respectively. Cerebral blood flow studies (stable xenon computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, dialysate potassium values were increased (dialysate potassium > 1.8 mM) for 3 hours or more. A mean amount of dialysate potassium greater than 2 mM throughout the entire monitoring period was associated with ICP above 30 mm Hg and fatal outcome, as were progressively rising levels of dialysate potassium. The presence of dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate (p < 0.0001) levels. Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). CONCLUSIONS: Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase in dialysate potassium, together with dialysate glutamate and lactate, supports the concept that glutamate induces ionic flux and consequently increases ICP, which the authors speculate may be due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered vasoreactivity in cerebral blood vessels caused by higher levels of potassium after trauma. Additional studies in which potassium-sensitive microelectrodes are used are needed to validate these ionic events more clearly.

High extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

Disturbed ionic and neurotransmitter homeostasis are now recognized to be probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brian injury (TBI). Evidence obtained from animal models indicates that posttraumatic neuronal excitation via excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with intracranial pressure (ICP), outcome, and also with the levels of dialysate glutamate, lactate, and cerebral blood flow (CBF) so as to determine the role of ischemia in this posttraumatic ionic dysfunction. Eighty-five patients with severe TBI (Glasgow Coma Scale score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed by flame photometry, as were dialysate glutamate and dialysate lactate levels, which were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients respectively. Cerebral blood flow studies (stable Xenon--computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, potassium values were increased (dialysate potassium > 1.8 mmol). Mean dialysate potassium (> 2 mmol) was associated with ICP above 30 mm Hg and fatal outcome. Dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate levels (p < 0.0001). Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase of potassium, together with dialysate glutamate and lactate, supports the hypothesis that glutamate induces ionic flux and consequently increases ICP due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered potassium reactivity in cerebral blood vessels after trauma.