Use of Alpha 1 blocker as a part of Medical Expulsive Therapy (MET) for Ureteric Stone

The traditional teaching has been plenty of water, control of infection and some anti-spasmodic as an expectant treatment for small ureteric stones, i.e. around 5 mm. in diameter, to pass out; more than 10 mm, requires intervention.

In the recent days, the management of ureteric stone has been revolutionalised by introduction of Extra-Corporeal Shock Wave Lithotripsy (ESWL) and ureteroscopic surgery /other minimally invasive surgeries.

However, there is always a room for conservative management of ureteric stones, where the size of stone is around 5 mm. in diameter and is located more towards the distal part of the ureter.

Migration and increase in size of stone causes excruciating pain, only known to those, who suffer from it.

An article published in Cleveland Clinic Journal of Medicine, based on the original article published in the BMJ (British Medical Journal, Alpha Blockers & Treatment of Ureteric Stones, BMJ; ePub 2016 Dec 1; Hollingsworth, et al. December 20, 2016) recommends use of Alpha 1 blocker as a part of Medical Expulsive Therapy (MET) for ureteric stone, precisely located more distally in the ureter.

Urinary stones are common, with a prevalence of about 5% in the population. Non-contrast CT scan is the diagnostic modality of choice. When calculi are smaller than 5 mm, 90% will pass spontaneously, but as stones approach 10 mm., there is less than a 10% chance that they will pass.

Since, small stones pass spontaneously almost all of the times, alpha-blockers add little to the management of these small stones. The value of alpha-blockers is for stones of 5 mm to 10 mm in size, where the use of an alpha-blocker significantly improves the rate of passage without surgical intervention.

When conservative management of a ureteral stone is being considered and the patient has no associated signs of infection, uncontrollable pain, or renal failure, adjuvant pharmacologic intervention has proven efficacious in improving spontaneous stone passage rate and time interval, and in reducing analgesic requirements.

Many of the studies have administered the drugs in conjunction with steroids and/or NSAIDs, which may reduce ureteral edema and improve the ability for a patient to spontaneously pass a ureteral stone.

However, several of the more recent studies have shown benefit to both α-blockers and calcium channel blockers without the adjunctive use of steroids; furthermore, tamsulosin, in randomized trials, has been shown to be more efficient than nifedipine with a decreased time to expulsion and slightly higher rate of expulsion.

Alpha-1-adrenergic receptors are located throughout the human ureter. The physiologic response to antagonism of these receptors is decreased force of contraction, decreased peristaltic frequency, and increased fluid bolus volume transported down the ureter. These responses are likely, how α-blockers assist in ureteral stone passage.

Alpha-blockers, specifically α1 antagonists, are highly effective in increasing the expulsion rate of distal ureteral stones, reducing the time to stone passage, and decreasing the amount of pain medication needed during passage stones.

Alpha blockers may also be a useful adjunct in the treatment of both ureteral and renal stones after ESWL. They may also reduce the urinary symptoms and pain associated with double-J ureteral stents. 

Main Points

• Medical expulsion therapy is a useful adjunct to observation in the conservative management of ureteral stones. 
• Alpha-1 receptors are located in the human ureter, especially the distal ureter; α-blockers increase expulsion rates of distal ureteral stones, decrease time to expulsion, and decrease need for analgesia during stone passage. Moderate quality evidence was observed that alpha blockers facilitate passage of ureteric stones. 
• In the appropriate clinical scenario, the use of α-blockers is recommended in the conservative management of distal ureteral stones. 
• The greatest benefit may be among patients with larger stones (57% higher likelihood of stone passage vs controls). 
• Compared with controls, patients receiving alpha blockers had significantly shorter times to stone passage, fewer episodes, lower risks of surgical intervention, and lower risk of admission to hospital.

Urinary stone disease is frequently seen in the urology practice. Symptoms include flank or abdominal pain radiating to the groin or external genitalia. Although some patients with ureteral stones might remain asymptomatic, many have pain and thus commonly seek medical care. Ureteric stone and its' size are best assessed in a non-contrast CT in comparison to the ultrasound examination.

An acute episode of colic is the result of a stone entering the ureter and causing intermittent rise of pressure in the pyelocalyceal system. Spontaneous passage will occur in most of these stones. 

An review article published in Cochrane Library (2nd April, 2014, Authors: Campschroer T, Zhu Y, Duijvesz D, Grobbee DE, Lock M) identified 32 studies enrolling 5864 participants. The use of alpha-blockers in patients with ureteral stones resulted in a higher stone-free rate and a shorter time to expulsion and therefore decreased the duration of symptoms and rate of complications (UTI, hydronephrosis and impairment of kidney function).

Medical expulsive therapy includes the use of oral/intravenous hydration, analgesics, and medications that promote stone passage, including alpha-1 blockers.

The most common alpha-1 blocker used to aid in the passage of ureteral stones is tamsulosin. The indicated use for tamsulosin is for treating symptoms of benign prostatic hyperplasia (BPH) (Alexander, 2010); however, off-label use has recently emerged as an efficacious and safe option for the initial management of ureteral stones (Bensalah et al., 2008)

Tamsulosin may help patients pass a kidney stone by relaxing the smooth muscle of the intramural ureters, allowing urine and stones to pass through more easily.

Tamsulosin is an antagonist of alpha1Aadrenoreceptors in smooth muscle; blocking them leads to relaxation of smooth muscle in the bladder neck causing an improvement in urine flow (Alexander, 2010).

Tamsulosin also relaxes the smooth muscle of veins and arteries, which can cause patients to feel dizzy when getting up from a sitting or lying position (orthostatic hypotension). Patients who take tamsulosin should be careful not to move too quickly when changing positions to avoid dizziness or syncopy.

Other documented side or adverse effects include blurred vision, cough, decreased sexual function, diarrhea, dizziness, drowsiness, lightheadedness, runny or stuffy nose, sinus in flam mation, trouble sleeping, and weakness (Lexi-Comp, Inc., 2011). Overdose symptoms include clammy or cold skin, rapid heartbeat, lightheadedness, extreme headache, and passing out.

Because of its sustained release formulation, the manufacturer does not recommend opening, crushing, or chewing the capsule/tablet because this can increase the medication's potential side effects (Alexander, 2010). Patients with a sulfa allergy should not use tamsulosin as a cross reactivity has been noted (Lexi-Comp, Inc., 2011)

Most adverse effects were mild of origin and did not lead to cessation of therapy, and several studies reported no adverse events in either the treatment or control group.

Alpha-blockers could be considered as first-line treatment for patients presenting with urinary stones.

All the Patients of Acute Myocardial Infarction (STEMI) may not require Oxygen therapy

Oxygen therapy has been a mandatory requirement for more than 100 years unquestionably, to treat acute heart attack, i.e. Myocardial Infarction, most of the times on the basis of anecdotal evidence, expert opinion, and tradition. Recent compelling evidences have challenged this conventional thinking.

myocardial infarction - Myokardinfarkt - scheme (Photo credit: Wikipedia)

Immediate treatment with Morphine, oxygen, nitrates and antiplatelets (MONA) has become the standard treatment for acute myocardial infarction (AMI) patient. Oxygen is a lifesaving drug. Giving oxygen to patient with impending clinical emergency has become knee-jerk reflex reaction of clinician. At the same time, if not provided immediately, raises many questions from all the quarters including patient and his attendants.

Patient with AMI has compromised myocardial perfusion and event arises due to myocardial hypoxia. It appears quite logical and biologically plausible to give oxygen in such situations to improve the oxygenation of the ischemic myocardial tissue and decrease ischemic pain.
On the other side, oxygen may be harmful for its’ paradoxical effect in decreasing coronary artery blood flow and increasing coronary vascular resistance, evidenced by intra-coronary Doppler ultrasonography. This effect leads to decrease in cardiac output and stroke volume. Excess Oxygen in blood (hyperoxia) causes increase in vascular resistance and reperfusion injury due to increased oxygen free radicals.
A survey among doctors managing AMI cases had showed that oxygen supplementation was given to 96% of their patients with acute coronary syndrome. About 50% of participants believed that oxygen reduces fatality, 25% thought it is helpful in decreasing pain, and 25% thought it has no effect.
Researchers like, Nicholson, Beasley et al. and Wijesinghe et al. have suggested that efficacy and safety of high flow oxygen in MI is not substantial. The existing evidence suggests that the routine use of high flow oxygen in uncomplicated MI can cause greater infarct size and possibly increase the risk of mortality.
Cochrane systemic review by Cabello et al., did not find any conclusive evidence from randomized controlled trials (four parallel-design, randomized controlled trials reported between 1976 and 2012) to support the routine use of inhaled oxygen in patients with acute AMI.
Recently published, Air Verses Oxygen in myocardial infarction study (AVOID Study) suggested routine oxygen supplementation to AMI patients from the ambulance through to the recovery room might actually be hurting their hearts. AVOID was a randomized, controlled, multicenter trial with the aim of comparing oxygen supplementation (6–8 L/min) with no oxygen in STEMI patients with oxygen saturation in the normal range pulse oximetry saturation >94%.
The study found a significant 25% increase in creatine kinase, suggestive of increased myocardial injury and cardiac magnetic resonance imaging (cardiovascular magnetic resonance) at 6 months suggestive of larger infarction size with oxygen therapy. Although, the mortality was similar in both groups, significant increases in recurrent MI and arrhythmias were observed in the oxygen group. Even though, AVOID Study used higher oxygen flow 6–8 L/min (more than usual clinical practice) and study was not powered for hard clinical end points, AVOID trial would really question the current practice of oxygen supplementation to all patients with acute myocardial ischemia and definitely to those with normoxia.
This subject is being further studied by researchers with the Swedish Coronary Angiography and Angioplasty Registry in an open-label randomized trial DETO₂ X-AMI (with more than 5000 enrolled patients in multi centres) with mortality as the primary endpoint. Results are awaited which may have definitive conclusive evidence.
American Heart Association Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care recommends oxygen in patients with dyspnea, hypoxemic, or with signs of heart failure and shock, based on monitoring of oxy-hemoglobin saturation, to ≥94%. However, evidence to support oxygen use in uncomplicated acute coronary syndromes is inadequate.
Oxygen overdose is not a new, but the way we use oxygen in coronary emergency needs reconsideration. Time has come to reassess oxygen treatment in acute coronary syndrome. Clinical practice should be based on proven benefits and safety, not on tradition. Oxygen is a life-saving drug and how much you give the patients, depends on how much they need.
The question of oxygen administration to all patients of AMI remains unanswered until new strong evidence comes.
The original article can be accessed here.