[Intraoperative management of potentially fatal arrhythmias after anesthesia induced by severe hypokalemia: A case report].

Severe hypokalemia is defined as the concentration of serum potassium lower than 2.5 mmol/L, which may lead to serious arrhythmias and cause mortality. We report an unusual case of potentially fatal ventricular arrhythmias induced by severe hypokalemia in a patient undergoing laparoscopic partial nephrectomy in Peking University Third Hospital due to irregular use of indapamide before operation. Indapamide is a sulfonamide diuretic with vasodilative and calcium antagonistic effects, which enhances sodium delivery to the renal distal tubules resulting in a dose-related increase in urinary potassium excretion and decreases serum potassium concentrations. The electrolyte disorder caused by the diuretic is more likely to occur in the elderly patients, especially those with malnutrition or long-term fasting. Hence, the serum potassium concentration of the patients under indapamide therapy, especially elderly patients, should be monitored carefully. Meanwhile, the potassium concentration measured by arterial blood gas analysis is different from that measured by venous blood or laboratory test. According to the previous research, the concentration of potassium in venous blood was slightly higher than that in arterial blood, and the difference value was 0.1-0.5 mmol/L. This error should be taken into account when rapid intravenous potassium supplementation or reduction of blood potassium level was carried out clinically. In the correction of severe hypokalemia, the standard approach often did not work well for treating severe hypokalemia. The tailored rapid potassium supplementation strategy shortened the time of hypokalemia and was a safe and better treatment option to remedy life-threatening arrhythmias caused by severe hypokalemia with a high success rate. Through the anesthesia management of this case, we conclude that for the elderly patients who take indapamide or other potassium excretion diuretics, the electrolyte concentration and the general volume state of the patients should be comprehensively measured and fully evaluated before operation. It may be necessary for us to reexamine the serum electrolyte concentration before anesthesia induction on the morning of surgery in patients with the history of hypokalemia. For severe hypokalemia detected after anesthesia, central venous cannulation access for individualized rapid potassium supplementation is an effective approach to reverse the life-threatening arrhythmias caused by severe hypokalemia and ensure the safety of the patients.

Intraoperative management of potentially fatal arrhythmias after anesthesia induced by severe hypokalemia: A case report / 北京大学学报(医学版)

Severe hypokalemia is defined as the concentration of serum potassium lower than 2.5 mmol/L, which may lead to serious arrhythmias and cause mortality. We report an unusual case of potentially fatal ventricular arrhythmias induced by severe hypokalemia in a patient undergoing laparoscopic partial nephrectomy in Peking University Third Hospital due to irregular use of indapamide before operation. Indapamide is a sulfonamide diuretic with vasodilative and calcium antagonistic effects, which enhances sodium delivery to the renal distal tubules resulting in a dose-related increase in urinary potassium excretion and decreases serum potassium concentrations. The electrolyte disorder caused by the diuretic is more likely to occur in the elderly patients, especially those with malnutrition or long-term fasting. Hence, the serum potassium concentration of the patients under indapamide therapy, especially elderly patients, should be monitored carefully. Meanwhile, the potassium concentration measured by arterial blood gas analysis is different from that measured by venous blood or laboratory test. According to the previous research, the concentration of potassium in venous blood was slightly higher than that in arterial blood, and the difference value was 0.1-0.5 mmol/L. This error should be taken into account when rapid intravenous potassium supplementation or reduction of blood potassium level was carried out clinically. In the correction of severe hypokalemia, the standard approach often did not work well for treating severe hypokalemia. The tailored rapid potassium supplementation strategy shortened the time of hypokalemia and was a safe and better treatment option to remedy life-threatening arrhythmias caused by severe hypokalemia with a high success rate. Through the anesthesia management of this case, we conclude that for the elderly patients who take indapamide or other potassium excretion diuretics, the electrolyte concentration and the general volume state of the patients should be comprehensively measured and fully evaluated before operation. It may be necessary for us to reexamine the serum electrolyte concentration before anesthesia induction on the morning of surgery in patients with the history of hypokalemia. For severe hypokalemia detected after anesthesia, central venous cannulation access for individualized rapid potassium supplementation is an effective approach to reverse the life-threatening arrhythmias caused by severe hypokalemia and ensure the safety of the patients.

Perindopril/Indapamide/Amlodipine in Hypertension: A Profile of Its Use.

The single-pill combination (SPC) of perindopril (PER)/indapamide (IND)/amlodipine (AML) is a valuable and convenient treatment option for patients with hypertension controlled with two-drug SPC of PER/IND + AML given as two separate pills at the same dose level. PER [an angiotensin-converting enzyme (ACE) inhibitor], IND (a thiazide-like diuretic) and AML (a calcium channel blocker) are well established antihypertensive agents, which have been available for a long time as monotherapies and dual SPCs and have complementary mechanisms of action. Once-daily PER/IND/AML provided effective BP control, with good tolerability, in patients with uncontrolled hypertension in clinical trials and in large observational prospective studies. The efficacy and tolerability of PER/IND/AML was similar to that of PER/IND + AML in a randomized clinical trial. The therapeutic effect of PER/IND/AML was associated with improved health-related quality of life. Thus, switching from the two-pill PER/IND + AML regimen to single-pill PER/IND/AML reduces pill burden and simplifies drug administration, which may improve adherence to treatment, leading to better BP control and clinical outcomes.

Approximately one-quarter of patients with hypertension require three antihypertensive agents to achieve BP control. However, complex treatment regimens and high pill burden reduce treatment adherence, which in turn leads to poor BP control. Perindopril (PER), indapamide (IND), amlodipine (AML) belong to the core drug classes for the treatment of hypertension. These drugs have been available for a long time as monotherapies and two-drug single-pill combinations. Once-daily PER/IND/AML provides very good BP control in patients with uncontrolled hypertension and is generally well tolerated. The single-pill PER/IND/AML has similar efficacy and tolerability to PER/IND + AML given as two separate pills. Therefore, switching from PER/IND + AML to PER/IND/AML reduces pill burden and simplifies the treatment regimen, which may improve adherence to treatment, leading to better BP control and clinical outcomes. Thus, PER/IND/AML is a valuable and convenient treatment option for patients with hypertension controlled with PER/IND + AML at the same dose level.

Impact of long-term potassium supplementation on thiazide diuretic-induced abnormalities of glucose and uric acid metabolisms.

Treatment of hypertension with thiazide diuretics may trigger hypokalemia, hyperglycemia, and hyperuricemia. Some studies suggest simultaneous potassium supplementation in hypertensive patients using thiazide diuretics. However, few clinical studies have reported the impact of long-term potassium supplementation on thiazide diuretic-induced abnormalities in blood glucose and uric acid (UA) metabolisms. One hundred hypertensive patients meeting the inclusion criteria were equally randomized to two groups: IND group receiving indapamide (1.25-2.5 mg daily) alone, and IND/KCI group receiving IND (1.25-2.5 mg daily) plus potassium chloride (40 mmol daily), both for 24 weeks. At the end of 24-week follow-up, serum K+ level in IND group decreased from 4.27 ± 0.28 to 3.98 ± 0.46 mmol/L (P < 0.001), and fasting plasma glucose (FPG) and UA increased from 5.11 ± 0.52 to 5.31 ± 0.57 mmol/L (P < 0.05), and from 0.404 ± 0.078 to 0.433 ± 0.072 mmol/L (P < 0.05), respectively. Serum K+ level in IND/KCl group decreased from 4.27 ± 0.36 to 3.89 ± 0.28 mmol/L (P < 0.001), and FPB and UA increased from 5.10 ± 0.41 to 5.35 ± 0.55 mmol/L (P < 0.01), and from 0.391 ± 0.073 to 0.457 ± 0.128 mmol/L (P < 0.001), respectively. The difference value between the serum K+ level and FPG before and after treatment was not statistically significant between the two groups. However, the difference value in UA in IND/KCl group was significantly higher than that in IND group (0.066 (95% confidence interval (CI): 0.041-0.090) mmol/L vs. 0.029 (95% CI: 0.006-0.058) mmol/L, P < 0.05). The results showed that long-term routine potassium supplementation could not prevent or attenuate thiazide diuretic-induced abnormalities of glucose metabolism in hypertensive patients; rather, it may aggravate the UA metabolic abnormality.

Prospective direct comparison of antihypertensive effect and safety between high-dose amlodipine or indapamide in hypertensive patients uncontrolled by standard doses of angiotensin receptor blockers and amlodipine.

OBJECTIVE: When hypertension is uncontrolled by routine treatment with an angiotensin II receptor blocker (ARB) and the calcium channel blocker amlodipine (5 mg), the dose of amlodipine can be increased or a diuretic can be added. We investigated the more effective option in a prospective multicenter open-label study. METHODS: Hypertensive patients were recruited if the target blood pressure (BP) in The Japanese Society of Hypertension 2009 guideline could not be achieved with standard-dose ARB therapy and amlodipine (5 mg). PATIENTS: Patients were divided into three groups. Group-1 was switched to a combination of irbesartan (100 mg) and amlodipine (10 mg). Group-2A was changed to a combination of irbesartan (100 mg), amlodipine (5 mg), and indapamide, while Group-2B received a standard-dose ARB and amlodipine (5 mg) plus indapamide. Patients were assigned by their attending physicians and were followed for 6 months. The primary endpoint was the antihypertensive effect of each regimen. RESULTS: Group-1 contained 85 patients, Group-2A had 49 patients, and Group-2B had 4 patients. We only analyzed Group-1 and Group-2A due to the small size of Group-2B. In both groups, systolic BP and diastolic BP were significantly decreased up to 6 months (all p < 0.001). Reduction of systolic BP was greater in Group-1 than Group-2A after 1 month and 6 months (both p < 0.05). Uric acid was increased in Group-2A after 3 months, but not at 6 months. CONCLUSION: Although both regimens were effective for reducing BP, increasing amlodipine to 10 mg daily controlled hypertension without elevation of serum uric acid.

[Fixed dose combination perindopril-indapamide-amlodipine (Triplixam) for the treatment of arterial hypertension]. / Combinaison fixe périndopril-indapamide-amlodipine (Triplixam) pour le traitement de l'hypertension artérielle.

Triplixam is a fixed dose combination of three well known antihypertensive agents, with complementary activities, to control blood pressure in patients with arterial hypertension: perindopril, an angiotensin converting enzyme inhibitor, indapamide, a diuretic whith thiazide-like effects but also specific properties, and amlodipine, a long-acting calcium antagonist of the dihydropyridine family. The potential synergic action allows better control of blood pressure with once daily administration, while limiting the incidence of adverse events. Various presentations with different dosages are available to facilitate individualized therapy. Warnings and precautions for use of every molecule should of course be respected. Such a fixed dose combination should contribute to limit clinical inertia and to improve therapeutic compliance.

A case of hypokalemia-induced fatal arrhythmia caused by indapamide in an anorexic elderly patient.

An 84-year-old man was referred to our hospital for atrioventricular block and severe hypokalemia. He had been treated for hypertension since 2007 with indapamide, a thiazide-like diuretic. His laboratory data had not been tested for a long time. One week before his first visit, he suffered from a common cold and anorexia. He was admitted to our hospital because his electrocardiogram showed ventricular flutter, and pulmonary arrest occurred at the time of his visit. Cardiopulmonary resuscitation was successfully performed. Hypokalemia (K, 1.7 mEq/L) was considered as the cause of acute cardiopulmonary failure. His oral intake of potassium decreased, but potassium loss from the kidney persisted (urinary potassium, 14.0 mEq/L; transtubular potassium gradient, 5.00). These results suggested that although hypokalemia was suspected to have been present for a long time due to indapamide, severe hypokalemia was induced during the period of anorexia. After discontinuation of indapamide and intravenous administration of potassium L: -aspartate for potassium supplementation, the patient's serum potassium levels increased and his general condition improved. Although it is well known that hypokalemia is caused by indapamide, the incidence is not frequent and if observed is not severe. However, we experienced an unusual case of hypokalemia-induced fatal arrhythmia caused by indapamide. Hence, the serum potassium concentration of patients under the drug, especially anorexic elderly patients, should be monitored.

Evaluation of high dose of perindopril/indapamide fixed combination in reducing blood pressure and improving end-organ protection in hypertensive patients.

BACKGROUND: Despite the widespread notion that controlling hypertension is essential to improve cardiovascular outcome, uncontrolled hypertension rates remain high. Fixed-dose combinations are used routinely to reduce the impact of hypertension. Treatment with fixed-combination perindopril/indapamide, for example, at the currently approved doses (perindopril 2 mg/indapamide 0.625 mg [Per2/Ind0.625] and perindopril 4 mg/indapamide 1.25 mg [Per4/Ind1.25]), reduces blood pressure, end-organ damage, and cardiovascular morbidity and mortality in a wide range of hypertensive patients. AIM AND SCOPE: This article reviews three published randomised trials that evaluated the efficacy and safety of the highest dose of perindopril/indapamide (perindopril 8 mg/indapamide 2.5 mg [Per8/Ind2.5]) in blood pressure lowering and end-organ protection studies. RESULTS: In the first (dose-finding) study, incremental reductions in SBP/DBP were observed with each dose doubling. After 8 weeks of treatment, decreases in supine SBP/DBP were statistically significant compared to placebo for all three doses, with incremental and progressive reductions with each dose doubling: ranging from SBP/DBP respectively -14/-9 mmHg for Per2/Ind0.625 to -23/-15 mmHg for Per8/Ind2.5 compared to -5/-5 mmHg for placebo. In the PICXEL and PREMIER trials, SBP/DBP decreases of 16.3/8.1 mmHg (p < 0.0001) and 2.5/2.6 mmHg, respectively, were noted when Per4/Ind1.25 was doubled to Per8/Ind2.5 (decreases from 167.7/101.7 to 151.4/93.6 in PICXEL and from 154.9/92.1 to 152.4/89.5 in PREMIER, respectively). As a consequence more patients had normalised blood pressure (22% and 17%), more patients responded to treatment (68% and 45%), and 29% and 10% of non-responders became responders, in PICXEL and PREMIER, respectively. Additional end-organ benefits were also noted with Per8/Ind2.5. In PICXEL, significant decreases from baseline in left ventricular mass were noted with all three doses, with a 17.5 g/m(2) decrease from baseline in patients whose maximum dose was Per8/Ind2.5 (from 148.5 g/m(2) +/- 39.5 (mean +/- SD) to 131 g/m(2); p < 0.0001). In PREMIER, changes in albumin excretion rate were also noted with all three doses, with a 45% reduction from baseline in patients whose maximum dose was Per8/Ind2.5 (p < 0.0001). When safety data, including potassium levels, were analysed, the increase in dose to Per8/Ind2.5 did not have a notable impact on the safety profile of perindopril/indapamide. CONCLUSIONS: Based on data available from an evaluation of three randomised clinical trials, fixed-combination Per8/Ind2.5 provided a significant, incremental reduction in blood pressure as well as cardiac and renal end-organ protection while remaining safe and well-tolerated.

Hyperlipidemia of diuretic therapy.

Hyperlipidemia is a widely acknowledged side effect of thiazide diuretic therapy, but it is often dismissed as a short-term effect of high-dose therapy. Large clinical trials usually show no lipid change during late follow-up. These large trials use intention-to-treat analysis which masks the lipid effect. On-treatment analysis regularly reveals the persistence of hyperlipidemia during 4-5 years of treatment. Studies of low-dose thiazide therapy give conflicting results. Meta-analysis of these studies reveals hyperlipidemia of a milder degree than with high-dose thiazide treatment. However, a trade-off of effects is apparent because systolic blood pressure is lowered less well with low doses. Thus, thiazide effects on blood pressure and lipids are dose-dependent. Similar meta-analysis of indapamide 2.5 mg daily shows no adverse lipid effect and a lowering of blood pressure equivalent to 50 mg of hydrochlorothiazide. Regarding clinical events, low-dose thiazide treatment exerts primary prevention of coronary heart disease but provides less benefit against stroke and congestive heart failure than does high-dose therapy. Thus, an evidence-based therapeutic strategy for further reducing cardiovascular risk is as follows: initiate antihypertensive therapy with low-dose diuretics. Add beta-blockers and dihydropyridine-type calcium channel blockers for further antihypertensive effect, if needed. Hypertension resistant to a 3-drug regimen should be treated with high-dose thiazides. Lipids should be monitored at each step and treated with diet and statin drugs to maintain lipid goals. Risk factor control is an old concept that has yet to be effectively implemented.

Clinical evaluation of muzolimine and indapamide during treatment for essential hypertension.

Muzolimine, a new saliuretic, has been shown to combine high ceiling and long-acting effects in animal experiments. This study was designed to examine whether this desirable combination of effects, which up until the present time has not been incorporated into any substance also occurs during patient treatment. Fifty-three patients with mild essential hypertension (WHO groups I and II) in three medical centers were treated with either muzolimine or indapamide, which served as the reference preparation, in a randomised, double-blind study. After a two week run-in phase during which the patients received placebo, half of the patients received 20 mg muzolimine and the other half 2.5 mg indapamide once daily. Eight weeks of therapy were followed by a 2 week follow-up phase, during which placebo was dispensed. During the trial period a weekly clinical examination was performed including the measurement of blood pressure, pulse, hematocrit, electrolytes, uric acid, glucose, creatinine and lipid status. An electrocardiogram and Schellongtest were conducted every two weeks. Patients were instructed to keep a diary in which they were to note drug related complaints. Statistical analysis was carried out using the Pratt-Wilcoxon Pair Test. Differences were judged significant at the 5% level. Both muzolimine and indapamide were tolerated well with minimal side effects, which however, did not make it necessary to discontinue treatment. Both preparations induced mild blood pressure reductions of approximately 10 and 5 mmHg for the systolic and diastolic blood pressure, respectively. Two weeks after cessation of muzolimine treatment neither systolic nor diastolic blood pressure showed any significant difference to values achieved during the treatment phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical efficacy and safety of indapamide in essential hypertension.

Indapamide, a new methylindoline diuretic that appears to act on the distal renal tubules, is also reported to reduce vascular smooth muscle vasopressor reactivity and possibly to have a calcium-antagonist effect. Since 1973, sixteen studies by a number of European investigators who treated 301 patients with indapamide have revealed satisfactory control in 53% of patients with mild hypertension (standing diastolic pressures less than 90 mm Hg) and in 43% of patients with moderate hypertension when the drug was used without other agents. Multiple American clinical trials of indapamide in hypertension have been conducted, including double-blind, placebo-controlled protocols and trials comparing indapamide with traditional diuretic agents. A cooperative, double-blind, 40-week study compared antihypertensive response to indapamide, 2.5 mg and 5 mg daily, with response to hydrochlorothiazide, 50 mg daily, in the treatment of mild to moderate hypertension. Pretreatment diastolic blood pressures averaged 101 mm Hg. At 40 weeks of treatment, indapamide, 2.5 mg daily, had produced a fall in diastolic pressure of 15 mm Hg; indapamide, 5 mg daily, a reduction of 16 mm Hg; and hydrochlorothiazide, 50 mg daily, a fall of 15 mm Hg. Seventy-five percent of patients taking 2.5 mg of indapamide daily and 88% of those taking 5 mg achieved satisfactory blood pressure reduction. Hypokalemia may occur with indapamide but is a minor problem and seldom necessitates potassium supplementation. Serum uric acid increases were observed in only a few subjects, and clinical side effects are infrequent and mild. Indapamide is a useful antihypertensive agent with good patient tolerance in mild or moderate hypertension and may offer advantages over traditional diuretics in view of its possible vasodilator and calcium-antagonist properties, once-a-day dosage, and good therapeutic effect with prolonged usage.

A comparative study of the activity of a new agent, indapamide, in essential arterial hypertension.

A single-blind crossover trial was carried out in 38 elderly, hospitalised patients with essential hypertension to compare the hypotensive activity of 5 mg. indapamide daily with 100 mg. chlorthalidone daily. After initial treatment for 10 days with placebo, patients received treatment for 45 days with either indapamide or chlorthalidone and were then crossed over to the alternative drug for a similar period. Potassium supplementation was necessary in 25 of the patients receiving chlorthalidone, but was precribed as a precautionary measure in only 1 patients whilst on indapamide. Results showed that there were significant drops in blood pressure following both active medications, but that the percentage reduction in diastolic pressure was greater after indapamide. Indapamide also proved more effective than chlorthalidone in controlling the patients' subjective and functional symptoms of their hypertension. In an overall assessment of the effectiveness of both drugs, indapamide was judged to be better tolerated as well as more effective than chlorthalidone in 18 of the 38 patients, whilst chlorthalidone was preferred in only 7 instances.