Hypertension (HTN) - Part of a Book PDF

Hypertension (HTN) LEARNING OBJECTIVES ------------------- - Outline the presentations of essential HTN - Identify the complications of uncontrolled hypertension - Specify the Diagnosis of HTN and therapy targets according to new guidelines - List the treatment of hypertension -...

Hypertension (HTN) LEARNING OBJECTIVES ------------------- - Outline the presentations of essential HTN - Identify the complications of uncontrolled hypertension - Specify the Diagnosis of HTN and therapy targets according to new guidelines - List the treatment of hypertension - Differentiate the types of secondary HTN - State the Diagnosis and treatment of hypertensive emergency Roughly one-third of the hypertensive population are unaware that they have high BP. This is mainly because 90--95 % have essential (primary) hypertension; that is, without an obvious cause or prominent symptoms. The remaining percentage is due to secondary causes. ESSENTIAL HYPERTENSION: {#essential-hypertension.headingsub} ----------------------- Essential hypertension is best thought of as a syndrome with many causes, not a single disease. Causes in each patient vary: *arterial stiffening, increased sodium sensitivity, or increased renin/angiotensin/aldosterone axis activity*. This variability means that each patient will respond differently to a given intervention or medication. Epidemiologically, essential hypertension is: - More common with *increasing age* (found in 50% of those age \>60) - More common in *obese* patients - *Men* \> women until after *menopause* - More common in *black* population at all ages, as is incidence of organ damage - Onset usually at the *age of 25--55 years* Diagnosis: {#diagnosis.o6ufirstheading} ---------- The definition of hypertension differs between international guidelines. Most agree that HTN is diagnosed when systolic BP exceeds 140 or diastolic BP exceed 90 mmHg. White coat Hypertension: {#white-coat-hypertension.o6ufirstheading} ------------------------ As much as 20--25% of mild office hypertension is not actually correct as these patients may have anxiety to the doctor/medical environment (known as "white coat hypertension"). These patients do not have evidence of end-organ damage. Out-of-Office monitoring can help to confirm this diagnosis, using either **Home BP monitoring or Ambulatory BP monitoring.** Thus, patients, especially with mildly elevated BP, should not be labelled as hypertensive after only a single reading: they can be advised for healthy lifestyle and repeat the readings over several months before confirming the diagnosis and initiating therapy. Classification of Hypertension: {#classification-of-hypertension.o6ufirstheading} ------------------------------- The commonly used classification (from European society of Cardiology) is shown in the table below, updated 2024: ***Category*** **systolic** **diastolic** ----------------------- -------------- ----- --------------- ***Non-elevated BP*** \ - Urinalysis for albuminuria, RBCs (screen for hypertensive nephrosclerosis and other renal diseases as secondary cause) - Serum potassium (to exclude hyperaldosteronism as a secondary cause) - Serum creatinine and BUN (screen for hypertensive nephrosclerosis and other renal diseases as secondary causes) - Serum glucose and plasma lipid analysis as an indicator of atherosclerotic risk ECG and Echocardiography: should be done to evaluate for left ventricular hypertrophy and ischemic changes {#ecg-and-echocardiography-should-be-done-to-evaluate-for-left-ventricular-hypertrophy-and-ischemic-changes.o6ufirstheading} ---------------------------------------------------------------------------------------------------------- Treatment: {#treatment.o6ufirstheading} ---------- - The ultimate goal of preventing and treating elevated BP and hypertension is to reduce CVD, to improve quality of life, and to prevent premature death. Crucially, besides BP, other CVD risk factors need to be comprehensively addressed (e.g. smoking, glucose, dyslipidaemia) - The target BP vary depending on other patient risk factors and age and usually takes 3-6 months to be attained. - To reduce CVD risk, it is recommended that treated systolic BP values in most adults be targeted to 120-- 129 mmHg, provided the treatment is well tolerated. - However, in very old patients and those with previous orthostatic hypotension, personalized and more lenient systolic BP targets (e.g. \ - Treat those who have post-myocardial infarction or systolic CHF beta blockers and ACEI/ARBs. - Treat those with CKD with ACEI/ARBs. (Both ACE inhibitors and ARBs reduce albuminuria more than other BP-lowering drugs and are effective at delaying the progression of diabetic and non-diabetic CKD but caution with hyperkalemia) - Pregnancy: treat HTN with alpha-methyldopa, labetalol, hydralazine, or CCBs. ACE inhibitors and ARBs are absolutely contraindicated. Diuretics are relatively contraindicated. ANTI-HYPERTENSIVE MEDICATIONS: {#anti-hypertensive-medications.o6ufirstheading} ------------------------------ First-line agents {#first-line-agents.heading20} ----------------- - **[Thiazide and thiazide-like diuretics: ]** - E.g. Chlorthalidone, hydrochlorothiazide, metolazone, and indapamide - **Specific indications** include CHF, edematous states - **Side effects** include decreased potassium and magnesium; increased glucose, calcium, uric acid, LDL; and gynecomastia. - **Relative contraindications** include pre-diabetes and diabetes (worsens glucose tolerance), gout, hyponatremia, and hyperlipidemia. - **[ACE I:]** - e.g. enalapril, captopril, enalapril, lisinopril, and ramipril - **Specific indication** includes chronic kidney disease, diabetics with microalbuminuria (to prevent nephropathy), CHF (afterload reduction), and post myocardial infarction with low EF. - **Side effects** include cough, angioneurotic edema, neutropenia, hyperkalemia, taste disturbances, anaphylactoid reactions. - **Contraindications** include hyperkalemia (k\5.5 mg/dl), bilateral renal artery stenosis and pregnancy - **[ARBs:]** - e.g. losartan, candesartan, valsartan, telmisartan, and irbesartan. - **Specific indications**: same as ACE I - **Main side effects**: Hyperkalemia - **Contraindications** include hyperkalemia (k\5.5 mg/dl), and pregnancy - **[Calcium channel blockers: (see before)]** Second- and third-line agents: {#second--and-third-line-agents.heading20} ------------------------------ - [**Beta blockers**:] - E.g. bisoprolol, metoprolol, IV Labetalol (combined beta and alpha) - **Specific indications** include myocardial infarction or ischemic heart disease (first line), systolic CHF (first line), supraventricular arrhythmias including Af, migraine headache, glaucoma, and anxiety (resting tachycardia). - **Side effects** include bronchospasm, heart block, bradycardia, Raynaud phenomenon, depression, impotence, fatigue, decreased HDL, increased triglycerides, and hyperglycemia. - **Relative contraindications** include asthma, COPD, atrioventricular conduction defects, decompensated heart failure and diabetes (masking signs of hypoglycemia) - **Absolute contraindications** include cardiogenic shock, acute bronchospasm & heart block - [**Potassium-sparing diuretics**: ] - E.g. Spironolactone, eplerenone, amiloride, and triamterene. - **Specific indications** include edema, potassium wasting states, CHF (spironolactone and eplerenone), and cirrhosis (spironolactone). - **Side effects** include hyperkalemia and gynecomastia (spironolactone). - Relative contraindications include hyperkalemia - These agents are often paired with thiazides to neutralize hypokalemic effect. - **[Central-acting sympatholytics]**: - Include clonidine and methyldopa. - **Clonidine** Side effects include **depression**, fatigue, dry mouth, impotence, bradycardia, heart block, and memory loss. - **Methyldopa** produces Coombs-positive **hemolytic anemia**. - **[Direct vasodilators:]** - They include hydralazine and minoxidil. - Hydralazine is used in eclampsia and with nitrates for some patients with systolic CHF. - **Side effects** include a ***lupus-like syndrome (hydralazine)*** and marked fluid retention, pericardial effusion, and hirsutism (minoxidil). - **Relative contraindications** include angina pectoris (reflex tachycardia). - **[Alpha-adrenergic blockers]:** - They include doxazosin, prazosin, and terazosin. - They are used for resistant HTN, prostatic hyperplasia and renal stones. - Side effects include *syncope after the first dose*, dizziness, and headache. Resistant Hypertension: {#resistant-hypertension.headingsub} ----------------------- **[Definition:]** Hypertension is defined as being treatment-resistant if BP is uncontrolled despite appropriate lifestyle measures and treatment with maximum or maximally tolerated doses optimal doses of at least three antihypertensive medications of different classes (usually including a diuretic) and after exclusion of various causes of pseudo-resistant hypertension (especially poor medication adherence). **Resistant hypertension is not a disease,** but an indicator that should be used to identify patients at high risk for CVD, in which secondary hypertension is also frequent. **[Causes of Pseudo-resistant hypertension:]** 1. Poor adherence to prescribed medicines 2. White-coat phenomenon 3. Poor office BP measurement technique 4. Inadequate doses of BP-lowering drug therapies. **[Causes of Resistant HTN:]** 1. Behavioural factors e.g. obesity, physical inactivity, excess dietary sodium, excess alcohol 2. Patient taking medications or herbs that elevate BP: a. **Medications Hormones e.g. contraceptive pills, cortisone, Nasal decongestants, NSAIDs, Immunosuppressives** b. **Ilicit drugs cocaine** c. **Herbs and foods liquorice عرق سوس, excess salt** 3. Undetected secondary HTN **[Diagnostic approach to resistant hypertension (assess for secondary causes and TOD):]** 1. The patient's history: including lifestyle characteristics, alcohol and dietary sodium intake, interfering drugs or substances, and sleep history. 2. The nature and dosing of the antihypertensive treatment, and check adherence. 3. A physical examination, with a particular focus on determining the presence of TOD and signs of secondary hypertension. 4. Confirmation of treatment resistance by out-of-office BP measurements 5. Laboratory tests to detect electrolyte abnormalities (hypokalaemia), associated risk factors (diabetes), organ damage (advanced renal dysfunction), and secondary hypertension. 6. Screen for secondary causes especially primary aldosteronism or atherosclerotic renal artery stenosis. {#section.headingsub} **[Recommended treatment of resistant hypertension:]** 1. Re-enforcement of lifestyle measures, especially sodium restriction. 2. Addition of other medications e.g. low-dose spironolactone, other diuretic therapy if intolerant to spironolactone, betablockers, doxazosin or other second and third line medications. 3. Sometimes, the patient may need device-based treatment e.g. Renal denervation therapy SECONDARY HYPERTENSION: {#secondary-hypertension.headingsub} ----------------------- Secondary hypertension (5% of all HTN cases) is hypertension due to an identifiable underlying cause. **Renal parenchymal disease, renovascular disease, obstructive sleep apnea and hyperaldosteronism** are among the most common cause in adults. **[When to suspect and screen for secondary hypertension?]** **[Presentation:]** With secondary hypertension, the presentation depends upon the cause. - Renovascular disease causes an abdominal bruit - Chronic kidney disease shows edema - Cushing disease causes weight gain, moon-like facies, striae, and ecchymoses - Primary hyperaldosteronism causes muscular weakness and polyuria/polydipsia from hypokalemia - Pheochromocytoma (very rare) causes episodic hypertension associated with headache, palpitations, and sweating The recommended lab work-up for essential hypertension will screen for the most common forms of secondary hypertension. A more intensive work-up can be done if there is a high clinical suspicion. Some of the causes will be discussed. 1. Renal artery stenosis: - May be unilateral or bilateral - Caused by *atherosclerotic disease* in patients with high CV risk or *fibromuscular dysplasia* in young women. - Physical exam may show an upper **abdominal bruit** radiating laterally (50--70% of patients). - Radiologic confirmation tests include: - Renal artery duplex U/S (best screening test) - Magnetic resonance angiography (equal to sonography in diagnostic ability but more expensive) usually done for confirmation - Renal arteriography (more invasive and used prior to surgical revascularization to confirm the extent of stenosis) - Treatment: - For bilateral disease: - The best initial treatment is percutaneous transluminal angioplasty with stenting. - If angioplasty fails, attempt surgical revascularization. - ACE inhibitors are effective for BP control; however, since they carry the risk of acute kidney injury in bilateral disease, use with caution. - For unilateral disease, ACE I, ?angioplasty 2. Chronic kidney disease (CKD) - Treatment emphasizes the use of ACE inhibitors (or ARB) for their effect in slowing progression of disease and reducing proteinuria. - Once on dialysis, effective fluid removal will improve the resistant hypertension seen in these patients. 3. Obstructive Sleep apnea: - Represent up to half the cases of secondary hypertension - Presentation includes snoring, breathing pauses during sleep and daytime sleepiness. - Patients usually obese - Diagnosis: Overnight oximetry, questionnaires, polysomnography - Treatment: CPAP or BiPAP during sleep. Some may require surgeries HYPERTENSIVE EMERGENCY: {#hypertensive-emergency.headingsub} ----------------------- A hypertensive emergency defined as BP of ≥180/110 mmHg associated with acute **end-organ damage**, often in the presence of symptoms. It is often life- threatening and requires immediate but careful intervention to lower BP, usually with intravenous (i.v.) therapy. Typical presentations of a hypertension emergency are: - Acute TOD e.g. stroke, encephalopathy, renal failure,... - Patients with **severe hypertension associated with other clinical conditions** who are likely to require an urgent reduction of BP, e.g. ***acute aortic dissection, acute myocardial ischemia, eclampsia or acute heart failure***. - **Malignant hypertension**, defined as extreme BP elevations and acute microvascular damage (microangiopathy) affecting various organs. The hallmark of this condition is small-artery fibrinoid necrosis in the kidneys, retina, and brain. The acute microangiopathy is typically characterized clinically by retinopathy (flame haemorrhages, cotton wool spots, and/or papilloedema). Other manifestations of microangiopathy include disseminated intravascular coagulation, encephalopathy (in about 15% of cases), acute heart failure, and acute deterioration in renal function. - Patients with sudden severe hypertension due to **phaeochromocytoma**, which can result in severe acute organ damage. Investigations: {#investigations.o6ufirstheading} --------------- - Lab evaluation is the same as for initial evaluation of essential hypertension - Head CT scan may be necessary to exclude hemorrhage. - ECG is important as an initial test to exclude infarction. - Other investigations that may be required: CT aortography for suspected dissection, Echocardiography and troponins for suspected infarction Treatment: {#treatment-1.o6ufirstheading} ---------- - Key considerations in defining treatment are: *(1)Establishing the affected target organ(s) and whether they require any specific interventions other than BP lowering.* *(2)Determining whether there is a precipitating cause for the acute rise in BP and/or another concomitant health condition present that might affect the treatment plan (e.g. pregnancy).* *(3)The recommended timing and magnitude of BP lowering required for safe BP reduction*. - In patients with acute ischaemic stroke, early BP lowering with BP-lowering therapy should be considered in the first 24 h in the following settings: - If eligible for re-perfusion therapy with intravenous thrombolysis or mechanical thrombectomy, BP should be carefully lowered and maintained at \ - Note: In evaluating patients with CHF, it is important to exclude precipitating factors. ***[Symptoms of HF: ]*** **Left sided failure** dyspnea, orthopnea, paroxysmal nocturnal dyspnea Right sided failure LL swelling and abdominal discomfort (hepatomegaly, ascites) Low cardiac output fatigue, dizziness The severity of heart failure is commonly classified by using The New York Heart Association Functional Classification (**[NYHA staging system]**) that depends on symptoms ONLY: (very important) - **[Class I:]** No limitation of activity; they suffer no symptoms from ordinary activities - **[Class II:]** Mild limitation of activity; they are comfortable with rest or with mild exertion - **[Class III:]** Marked limitation of activity; they are comfortable only at rest - **[Class IV:]** Any physical activity brings on discomfort and symptoms occur at rest ***[Physical findings in HF:]*** - Left sided failure Pulmonary rales/edema, in HFrEF (displaced apical impulse, Third heart sound and gallop, Mitral regurge murmur) - Right sided failure LL edema, Ascites, Hepatomegaly, Jugular venous distention - Low cardiac output hypotension, impaired capillary filling ACC/AHA Stages of HF: {#accaha-stages-of-hf.o6ufirstheading} --------------------- The ACC/AHA stages of HF recognize that both risk factors and abnormalities of cardiac structure are associated with HF whereas the NYHA classes focus on exercise capacity and the symptomatic status of the disease.. - ***Stage A:** patients at high risk of HF but without structural heart disease or symptoms e.g. Hypertension, dyslipidemia, obesity, DM,..* - ***Stage B:** patients with structural heart disease but without HF symptoms or signs e.g., MI, LVH, LV dysfunction, valvular heart diseases, (These can be in NYHA I)* - ***Stage C:** Patients with structural heart disease with prior or current HF symptoms (these can be in any NYHA class)* - ***Stage D:** Patients with refractory heart failure (NYHA IV)* Therapeutic interventions in each stage aimed at modifying risk factors (stage A), treating structural heart disease (stage B), and reducing morbidity and mortality (stages C and D). Investigations: {#investigations-1.o6ufirstheading} --------------- 1. **[Chest x-ray:]** It may show cardiomegaly, vascular redistribution, Kerley B-lines, or interstitial edema. It is also important to detect alternative cardiac, pulmonary, and other diseases that may cause or contribute to the patient's symptoms 2. **[ECG]**: may identify ventricular hypertrophy, the presence of ischemia, arrhythmias. 3. **[Brain natriuretic peptide (BNP)]** (or type B natriuretic peptide) and NT-pro BNP (N-terminal pro BNP): see clinical pathology section - *Remember that they have **very high sensitivity** (97% sensitivity): almost always elevated in patients with decompensated HF (except obesity, where BNP can be falsely low) but **low specificity** (elevated in many cardiac and non-cardiac conditions e.g. AF, cardiac surgery, pericardial diseases, pneumonia, pulmonary hypertension, sepsis, renal failure and old age) thus best used for ruling out HF* 4. **[Echocardiogram]**: determine ejection fraction (EF) and classify the type, and to identify valvular heart disease and other cardiac problems (dilated ventricle,......). 5. **[Other non-invasive imaging]** may be needed e.g. to rule out ischemia, to assess myocardial viability, or to diagnose some aetiological causes (infiltration,..) 6. **[Invasive procedures]** are sometimes needed: - Monitoring with a pulmonary artery catheter in patients with respiratory distress or impaired systemic perfusion when clinical assessment is inadequate - Coronary arteriography when ischemia may be contributing to HF - Endomyocardial biopsy can be useful in patients with HF when a specific diagnosis is suspected that would influence therapy e.g. amyloidosis Treatment of HFrEF: {#treatment-of-hfref.o6ufirstheading} ------------------- Treatment goals in HF are **to improve hemodynamics, relieve symptoms, and prolong survival.** A. Non-pharmacologic treatment: {#non-pharmacologic-treatment.heading20} ---------------------------- - Reduction of salt/fluid intake. - Specific education to facilitate HF self-care such as daily weighing and medication adherence - Moderation or stopping alcohol - Exercise training/cardiac rehabilitation: *Exercise training in patients with HF is safe and has numerous benefits. Meta-analyses show that cardiac rehabilitation may reduce mortality; improves functional capacity, exercise duration, and quality of life and reduces hospitalizations. Other benefits include improved endothelial function, blunted catecholamine spillover, increased peripheral oxygen extraction, and reduced hospital admission*. B. Pharmacologic treatment: (see details in pharmacology section): {#pharmacologic-treatment-see-details-in-pharmacology-section.heading20} --------------------------------------------------------------- {#section-1.heading20} Essential drugs (for all patients with HFrEF) The Four Pillars {#essential-drugs-for-all-patients-with-hfref-the-four-pillars.heading20} -------------------------------------------------------------- 1. **[ACE inhibitors or ARNI (]***angiotensin receptor-neprilysin inhibitor)***:** 2. **[Beta blockers]** 3. **[Sodium-glucose transport protein 2 (SGLT2) inhibitors]** *dapagliflozin or empagliflozin* 4. **[Aldosterone antagonists:]** *Spironolactone and eplerenone* and...... [ **Loop Diuretics:**] for relief of fluid retention {#section-2.heading20} Other drugs: {#other-drugs.heading20} ------------ - ***ARBs** if ACEI or ARNI are contraindicated* [ ] - ***Isosorbid dinitrate + Hydralazine** if ACEI or ARNI are contraindicated* - ***Digitalis*** - ***Ivabradine*** Cardiac Devices for HFrEF: {#cardiac-devices-for-hfref.heading20} -------------------------- After medical management has been initiated (at least for 3 months), several mechanical devices may be added to further improve symptoms and/or prognosis in HF. - ***[Automatic implantable cardioverter/defibrillator]*** (ICD) is a standard therapy for severe ischemic and nonischemic dilated cardiomyopathy (EF \ - Note: - ACE inhibitors/ARB, BBs, spironolactone/eplerenone, ARNI, SGLT2 inhibitors, AICD, and biventricular pacing all lower mortality in systolic CHF. - Digitalis and diuretics do not reduce mortality but help in management N.B. Management of Diastolic HF (HFpEF): {#n.b.-management-of-diastolic-hf-hfpef.o6ufirstheading} ---------------------------------------- Unfortunately, medications used for HFrEF failed to show significant mortality benefit in patients with HFpEF. Preferred management for HF with preserved systolic function includes the following: - Diuresis as needed for volume overload, but cautiously - Treatment of comorbidities e.g. BP - Exercise program and cardiac rehabilitation - BBs may help in rate control of Afib or if patient has concurrent CAD. - Recently, SGLT2 inhibitors showed promising results Acute Heart Failure (AHF): {#acute-heart-failure-ahf.headingsub} -------------------------- - AHF refers to *development of symptoms and/or signs of HF (usually rapid onset), severe enough for the patient to seek urgent medical attention, leading to an unplanned hospital admission or an emergency department visit*. - Patients with AHF require *urgent evaluation* with subsequent initiation or intensification of treatment, including i.v. therapies or procedures. - AHF may be the first manifestation of HF (new onset) or, more frequently, be due to an acute decompensation of chronic HF. (see **precipitating factors** above) - The diagnostic workup of AHF aims to *identify the clinical presentation* and to *diagnose and manage any potentially reversible causes/precipitants/coexisting life-threatening conditions* in a timely manner. - In addition to clinical signs and symptoms, diagnostic workup includes **ECG** and **echocardiography**, if possible. Additional investigations, i.e. **chest X-ray** and **lung ultrasound** may be used to confirm diagnosis. - **Plasma BNP** (or NT-proBNP) should be checked if available. - Other investigations may include: - TSH levels (Since both hypothyroidism and hyperthyroidism may precipitate AHF) - ABGs in patients with respiratory distress - D-dimer when acute pulmonary embolism is suspected. - Procalcitonin for pneumonia - Clinical assessment of patients is important and easy, to classify the patient into one of the following groups in the figure: (Two important presentations of AHF are: **Acute pulmonary edema and cardiogenic shock.) see figure** Patterns of presentation recognized in ADHF, as represented by a 2×2\... \| Download Scientific Diagram {#patterns-of-presentation-recognized-in-adhf-as-represented-by-a-22...-download-scientific-diagram.o6ufirstheading} ------------------------------------------------------------------------------------------------------- Figure showing clinical assessment of AHF Acute Cardiogenic Pulmonary edema: (warm and wet) {#acute-cardiogenic-pulmonary-edema-warm-and-wet.o6ufirstheading} ------------------------------------------------- - It is considered a medical emergency and requires hospitalization. Cardiogenic pulmonary edema is caused by an acute increase in L.V. pressure due to ventricular dysfunction, which leads to fluid accumulation in the pulmonary interstitium. - Clinical criteria for acute pulmonary oedema diagnosis include dyspnoea with orthopnoea, respiratory failure (hypoxaemia-hypercapnia), tachypnoea, and increased work of breathing. - Initial main therapies: 1. Oxygen given as continuous positive airway pressure, non-invasive positive pressure-ventilation and/or high-flow nasal cannula or even mechanical ventilation. 2. I.V. diuretics 3. I.V. vasodilators may be given if systolic BP is high, to reduce LV Afterload 4. If there is low cardiac output (cold and wet) inotropes, vasopressors, and/or MCS are indicated to restore organ perfusion. 5. Other medications: Morphine cautiously to avoid respiratory center depression. Routine use of opiates is not recommended Cardiogenic shock: (Cold and dry) {#cardiogenic-shock-cold-and-dry.o6ufirstheading} --------------------------------- - It is considered a medical emergency and requires hospitalization. Cardiogenic shock is a syndrome due to **primary cardiac dysfunction** resulting in an **inadequate cardiac output**, comprising a life-threatening state of **tissue hypoperfusion**, which can result in multiorgan failure and death. - Cardiac insult causing severe impairment of cardiac performance may be acute, as a result of the acute loss of myocardial tissue (acute MI, myocarditis) or may be progressive as seen in patients with chronic decompensated HF who may experience a decline in disease stability as a result of the natural progression of advanced HF and/or specific precipitants. - Diagnosis of cardiogenic shock requires the presence of clinical signs of **hypoperfusion**, such as *cold sweated extremities, oliguria, mental confusion, dizziness, narrow pulse pressure*. In addition, **biochemical manifestations of hypoperfusion**, **elevated serum creatinine, metabolic acidosis and elevated serum lactate** are present and reflect tissue hypoxia and alterations of cellular metabolism leading to organ dysfunction. - Management of cardiogenic shock should start as early as possible, including early identification and treatment of the underlying cause, haemodynamic stabilization and management of organ dysfunction. - IV vasopressors are usually initiated e.g. norepinephrine, epinephrine or high dose dopamine. Sometime a combination with dobutamine is used. N.B. IV Inotropes: **Phosphodiestrase inhibitors**: e.g., Imrinone and Milrinone - Use: acute CHF only, given as IV infusion - Increase cAMP in heart muscle, results in increase contractility. - Increase cAMP in smooth muscle, results in decrease in TPR. **Sympathomimetics:** - Dobutamine and Dopamine, IV infusions - -Use: acute CHF only SHOCK SYNDROMES LEARNING OBJECTIVES ------------------- - Enumerate the types of shock - List the different causes of each type of shock - Enumerate the main steps of management of shock Definition: {#definition-1.o6ufirstheading} ----------- Shock is a broad term that describes a state where oxygen delivery to the tissues is inadequate to meet the demands. It could be described as the imbalance between tissue oxygen supply and demand. General Types: see diagram {#general-types-see-diagram.o6ufirstheading} -------------------------- 1. Distributive shock: includes: sepsis (especially gram-negative), anaphylaxis, and neurogenic. All are associated with severe peripheral vasodilatation 2. Cardiogenic shock: related to impaired heart pump function 3. Hypovolemic shock: caused by decreased circulatory volume 4. Obstructive shock: non-cardiac obstruction to blood flow  {#types-of-shock---gram-project.o6ufirstheading} --------------------------------------------------- Management: {#management.o6ufirstheading} ----------- - **Airway protection and management of breathing** *Consider intubation for airway protection and to enhance ventilation and oxygenation.* - **Circulatory support** with normal saline in most types (except cardiogenic) - **Blood transfusion** in traumatic hypovolemic shock. - Hypotensive patients who do not respond to saline or blood will need **pressor support**: - **Norepinephrine** is the preferred vasopressor in septic and cardiogenic shock - Others include: Dopamine, vasopressin, or epinephrine - Gastric ulcer protection and DVT prophylaxis in most patients - **Other measures in selected patients:** Mechanical circulatory support, hydrocortisone, antibiotics, dobutamine, electrolyte correction, ,... Cardiovascular Pharmacology (2) **[Drugs For Heart Failure]** ----------------------------------------- **[Learning objectives:]** - Describe the primary treatments for CHF - Describe the main properties and side effects of the important medications especially digoxin and ACE I **[Aims of treatment:]** 1. **To ↓ preload (improves congestion):** - Diuretics e.g. loop diuretics - Venodilator e.g. nitrates *(or better mixed dilators e.g. ACEIs/ ARBs- Sodium nitroprusside)* 2. **To** ↓ **afterload (improves low COP)** - Arteriodilators e.g. hydralazine *(or better mixed dilators e.g. ACEIs/ ARBs- Sodium nitroprusside)* 3. **To** ↑ **contractility (improves low COP & congestion)** Positive inotropic drugs e.g. digoxin, dopamine, dobutamine 4. ***To protect the ventricles &* ↓ *mortality*** **[I. DIURETICS used in treatment of HF]** **Loop Diuretics** **(e.g. Frusemide or bumetanide)**: are of choice in most cases especially refractory or pulmonary edema where they are given by IVI. Oral absorption is limited because of gut edema. They also improve renal perfusion. **Potassium sparing diuretics** **(e.g. Spironolactone or eplerenone)**: are ineffective alone but are used in combination with loop diuretics to ↓ K-loss and ↑Na excretion. Spironolactone is specially indicated if there is 2^ry^ hyperaldosteronism. It is proved to improve patient survival by 25% if given for one year & by 40% if given for 2 years in patients with advanced HF. **Other diuretics** (e.g. thiazides or carbonic anhydrase inhibitors) may be used in refractoriness to loop diuretics [**II.** **VASODILATORS used in treatment of HF**] ***-Venodilators:* e.g. nitrates** → ↓ VR (venous return; preload) ---------------------------------------------------------------------------------------- *They decrease systemic or pulmonary congestion (i.e. improving congestive symptoms).* ---------------------------------------------------------------------------------------- **-Arteriodilators e.g. hydralazine** → ↓ PR (peripheral resistance; afterload) --------------------------------------------------------- *They increase COP (i.e. improve symptoms of low COP).* --------------------------------------------------------- ***-Mixed dilators: e.g. ACE I, ARBSs*** **[1) Angiotensin Converting Enzyme Inhibitors (ACEIs)]** **[Mechanism:]** - Vasodilatation of both arteries (↑ COP) and veins (↓ venous congestion) - Inhibition of aldosterone secretion (↓ Na and H~2~O retention) - Inhibition of cardiac remodeling **[Members:]** **Captopril**: it is the first to be discovered in this group, but t is short acting (t½\ 2. - Hypotension with first dose - Hyperkalemia: especially if the patient is receiving K-sparing diuretics. - Hypersensitivity: drug rash and pruritis - GIT adverse effects: anorexia, vomiting, diarrhoea & dysgeusia (metallic taste) 3. 4. - **Renal impairment:** it occurs in patients on aggressive diuretic therapy/ NSAIDs or in patients with bilateral renal artery stenosis (GFR is maintained by AGII). - **Bone marrow depression** (detected by white blood count) - **Teratogenic** (in the first trimester) & **Foetotoxic** (in the last trimester of pregnancy renal damage in the foetus. & newborn.