188 - Digitalis toxicity

*Reduced tolerance of digoxin may be seen in (factors predisposing to digitalis toxicity) :
 - Advanced age
- Acute Myocardial Infarction/ Ischemia/ Hypoxemia
- Magnesium depletion (hypomagnesemia)

- Hypercalcemia (Calcium synergises with digitalis and precipitates its toxicity)
- Hypothyroidism (Both hyperthyroidism and hypothyroidism enhance digitalis toxicity. Thyrotoxicosis patients are more prone to develop digitalis arrhythmias and Myxedema enhances responsiveness to digitalis. Myxedema patients eliminate digoxin more slowly)
- Renal insufficiency (Digoxin is mainly excreted by kidneys)

- Electrical cardioversion 

* Digitalis toxicity causes hyperkalemia, but hypokalemia enhances digitalis toxicity (by increasing its binding to Na+/K+ ATPase.

*The administration of the following drugs raises the serum concentration of digoxin :
- Quinidine
- Verapamil
- Procainamide
- Amiodarone

*MANAGEMENT OF DIGITALIS OVERDOSE :

- Withdrawl of the drug
- Potassium (administer cautiously and by oral route whenever possible if hypokalemia is present. Potassium must not be employed in the presence of A-V block or hyperkalemia.
- Phenytoin/Beta blocker or Lidocaine : Lidocaine is effective in treatment of digitalis induced ventricular tachyarrythmias.
- Cardiac pacemaker : may be required in digitalis induced A-V block.
- Electrical conversion : may be life saving in digitalis induced ventricular fibrillation 
- FAB fragments/ digitalis antibodies : are potentially life saving in severe intoxication 
- Hemodialysis is not useful in digoxin toxicity .

(Other conditions where hemodialysis is ineffective is Digoxin poisoning, Kerosene poisoning, Benzodiazepine poisoning and Organophosphate poisoning)

(Remember that Digoxin and Digitoxin are two different drugs, both derived from digitalis, But digitoxin is mainly excreted by liver and digoxin is mainly excreted by kidneys. Hence digoxin dosage need not be adjusted in liver failure and digitoxin dosage need not be adjusted in renal failure)

*The most lipid soluble cardiac glycoside is Digitoxin.
*The most rapidly absorbed oral glycoside is digitoxin.

187 - Metabolic syndrome - Clinical identification

Clinical Identification of the Metabolic Syndrome—Any Three Risk Factors

Risk Factor Defining Level Abdominal obesitya   Men (waist circumference)b >102 cm (>40 in.)   Women >88 cm (>35 in.) Triglycerides >1.7 mmol/L (>150 mg/dL) HDL cholesterol   Men <1.0 mmol/L (<40 mg/dL)   Women <1.3 mmol/L (<50 mg/dL) Blood pressure greater than or equal to 130/greater than or equal to 85 mmHg Fasting glucose >6.1 mmol/L (>110 mg/dL)

aOverweight and obesity are associated with insulin resistance and the metabolic syndrome. However, the presence of abdominal obesity is more highly correlated with the metabolic risk factors than is an elevated body-mass index (BMI). Therefore, the simple measure of waist circumference is recommended to identify the BMI component of the metabolic syndrome. bSome male patients can develop multiple metabolic risk factors when the waist circumference is only marginally increased, e.g., 94–102 cm (37–39 in.). Such patients may have a strong genetic contribution to insulin resistance. They should benefit from life-style changes, similarly to men with categorical increases in waist circumference.

186 - Pneumonia Severity Index (PSI) score or PORT score

*The decision to hospitalize a patient with CAP must take into consideration diminishing health care resources and rising costs of treatment. The cost of inpatient management exceeds that of outpatient treatment by a factor of 20 and accounts for most CAP-related expenditures.

*Certain patients clearly can be managed at home, and others clearly require treatment in the hospital, but the choice is sometimes difficult. Tools that objectively assess the risk of adverse outcomes, including severe illness and death, may minimize unnecessary hospital admissions and help to identify patients who will benefit from hospital care.

*There are currently two sets of criteria: the Pneumonia Severity Index (PSI), a prognostic model used to identify patients at low risk of dying; and the CURB-65 criteria, a severity-of-illness score.

*To determine the PSI, points are given for 20 variables, including age, coexisting illness, and abnormal physical and laboratory findings.

*On the basis of the resulting score, patients are assigned to one of five classes with the following mortality rates:

-class 1, 0.1%;

-class 2, 0.6%;

-class 3, 2.8%;

-class 4, 8.2%; and

-class 5, 29.2%.

*Clinical trials have demonstrated that routine use of the PSI results in lower admission rates for class 1 and class 2 patients. Patients in classes 4 and 5 should be admitted to the hospital, while those in class 3 should ideally be admitted to an observation unit until a further decision can be made.

*The CURB-65 criteria include five variables: 

1. Confusion (C); 

2. Urea >7 mmol/L (U); 

3. Respiratory rate greater than or equal to 30/min (R); 

4. Blood pressure, systolic less than or equal to 90 mmHg or diastolic less than or equal to 60 mmHg (B); and 

5. Age greater than or equal to 65 years (65). 

*Patients with a score of 0, among whom the 30-day mortality rate is 1.5%, can be treated outside the hospital.

*With a score of 2, the 30-day mortality rate is 9.2%, and patients should be admitted to the hospital.

*Among patients with scores of greater than or equal to 3, mortality rates are 22% overall; these patients may require admission to an ICU.

*At present, it is difficult to say which assessment tool is superior. The PSI is less practical in a busy emergency-room setting because of the need to assess 20 variables. While the CURB-65 criteria are easily remembered, they have not been studied as extensively. Whichever system is used, these objective criteria must always be tempered by careful consideration of factors relevant to individual patients, including the ability to comply reliably with an oral antibiotic regimen and the resources available to the patient outside the hospital.

185 - Drug induced Lupus

*This is a syndrome of positive ANA associated with symptoms such as fever, malaise, arthritis or intense arthralgias/myalgias, serositis, and/or rash.

*The syndrome appears during therapy with certain medications and biologic agents, is predominant in Caucasians, has less female predilection than SLE, rarely involves kidneys or brain, is rarely associated with anti-dsDNA, is commonly associated with antibodies to histones, and usually resolves over several weeks after discontinuation of the offending medication. 

*The list of substances that can induce lupus-like disease is long. Among the most frequent are the :

- Antiarrhythmics procainamide, disopyramide, and propafenone; 
- The antihypertensive hydralazine; several angiotensin-converting enzyme inhibitors and beta blockers; 
- The antithyroid propylthiouracil; 
- The antipsychotics chlorpromazine and lithium; 
- The anticonvulsants carbamazepine and phenytoin; 
- The antibiotics isoniazid, minocycline, and macrodantin; 
- The antirheumatic sulfasalazine; 
- The diuretic hydrochlorothiazide; 
- The antihyperlipidemics lovastatin and simvastatin; and 
- Interferons and TNF inhibitors. 

*ANA usually appears before symptoms; however, many of the medications mentioned above induce ANA in patients who never develop symptoms of drug-induced lupus.

*It is appropriate to test for ANA at the first hint of relevant symptoms and to use test results to help decide whether to withdraw the suspect agent.

184 - Effects of Physiological and Pharmacologic interventions on Heart Murmurs and sounds

Respiration Systolic murmurs due to TR or pulmonic blood flow through a normal or stenotic valve and diastolic murmurs of TS or PR generally increase with inspiration, as do right-sided S3 and S4. Left-sided murmurs and sounds usually are louder during expiration, as is the PES.

Valsalva maneuver Most murmurs decrease in length and intensity. Two exceptions are the systolic murmur of HCM, which usually becomes much louder, and that of MVP, which becomes longer and often louder. Following release of the Valsalva maneuver, right-sided murmurs tend to return to control intensity earlier than left-sided murmurs.

After VPB or AF Murmurs originating at normal or stenotic semilunar valves increase in the cardiac cycle following a VPB or in the cycle after a long cycle length in AF. By contrast, systolic murmurs due to AV valve regurgitation either do not change, diminish (papillary muscle dysfunction), or become shorter (MVP).

Positional changes With standing, most murmurs diminish, two exceptions being the murmur of HCM, which becomes louder, and that of MVP, which lengthens and often is intensified. With squatting, most murmurs become louder, but those of HCM and MVP usually soften and may disappear. Passive leg raising usually produces the same results.

Exercise Murmurs due to blood flow across normal or obstructed valves (e.g., PS, MS) become louder with both isotonic and submaximal isometric (handgrip) exercise. Murmurs of MR, VSD, and AR also increase with handgrip exercise. However, the murmur of HCM often decreases with near maximum handgrip exercise. Left-sided S4 and S3 are often accentuated by exercise, particularly when due to ischemic heart disease.

Note: TR, tricuspid regurgitation; TS, tricuspid stenosis; PR, pulmonic regurgitation; HCM, hypertrophic cardiomyopathy; MVP, mitral valve prolapse; PS, pulmonic stenosis; MS, mitral stenosis; MR, mitral regurgitation; PES, pulmonic ejection sound; VSD, ventricular septal defect; AR, aortic regurgitation; VPB, ventricular premature beat; AF, atrial fibrillation.

183 - First Heart Sound (S1)

*The first heart sound is otherwise called as S1.

*Its duration is 0.14 seconds.

*Its frequency is 25-45 Hz.

*Though S1 and S2, both are high pitched sounds, S1 has a lower frequency than S2. (50 Hz).

*The sound produced is a slightly prolonged "LUB".

*The cause of the first heart sound is the sudden closure of the mitral and tricuspid valves.

*The timing of the S1, is at the start of the ventricular systole.

*The first and second heart sounds, and the opening snaps are best heart with the diaphragm of the stethoscope, and low pitched sounds, such as the third and fourth heart sounds are best heard with the bell of the stethoscope.

*S3 and S4, can often not be heard with stethoscope (ear) and require phonocardiogram. S3 often and S4 sometimes can be recorded in phonocardiogram.

*CAUSES OF SOFT S1 :
1. Poor conductance of sound through chest wall. eg: Obesity, Ephysema, Pleural effusion and Pericardial effusion.
2. Decrease in rate of LV pressure development. eg: Myxoedema, Cardiomyopathy, Acute MI and MR.
3. PR interval and velocity of valve closure. eg: Prolonged PR interval - First degree heart block.
4. Mobility of the valve. eg: Severe calcification of the valve or reduced mobility of the valve - Long standing MS is associated with severe calcification of mitral valve and soft S1.

*CAUSES OF LOUD S1 :
1. Tachycardia : S1 is louder if diastole is shortened due to Tachycardia. eg: Anemia, anxiety and fever.
2. Increased AV flow due to high cardiac output. eg: AV fistula and thyrotoxicosis.
3. Increased AV flow due to left to right shunt. eg: ASD, PDA and other conditions.
4. Prolonged AV flow due to stenosis. eg: MS and TS.
5. Short PR interval (velocity of valve closure) - At short PR intervals, the mitral valve leaflets are maximally separated by atrial contraction. At the onset of LV systole, the mitral valve leaflets therefore close with a high velocity and with a large excursion resulting in loud S1.

*First Heart sound (M1,T1) is produced by the closure of the Mitral valves (M1) and Tricuspid valves (T1).

*The Mitral valves close slightly before the Tricuspid valves .

*This normal splitting (physiological splitting) cannot be detected by auscultation because both components are low pitched and separated by only 20-30 milliseconds.

*Therefore splitting of the first heart sound whenever audible, is considered pathological.

*CAUSES OF PATHOLOGICAL NORMAL SPLITTING OF S1 (T1 follows M1 after a long gap):
- RBBB (Right Bundle Branch Block)
- LV pacing
- Ectopic beats and idioventricular rhythms originating in left ventricle
- Ebstein's anamoly

*CAUSES OF PATHOLOGICAL REVERSE SPLITTING OF S1 (T1 precedes M1) :
- LBBB
- RV pacing
- Ectopic beats and idioventricular rhythms originating in right ventricle
- Severe MS and atrial myxoma

182 - Opportunistic infections in HIV