Hypokalaemic periodic paralysis in rural northern India – most have secondary causes

Introduction

Duncan Hospital sees around 30 patients with quadriparesis due to hypokalaemic periodic paralysis (HPP) each year. Here HPP, not Guillain-Barre syndrome, is the main cause of acute onset quadriparesis. ¹ Both ventricular arrhythmias and respiratory paralysis can cause death in patients with severe hypokalaemia.

In a clinical study of 68 patients at Duncan Hospital, North Bihar, in 1997, acute gastroenteritis (54%) was found to be the most common cause of HPP. There was no obvious underlying cause found in 38% of the patients in this study. ¹ In a study of 31 patients from Christian Medical College Vellore (a tertiary care centre) in 2006, the most common secondary causes of HPP were renal tubular acidosis (RTA) and primary hyperaldosteronism (42% each). ² In 2010, in another tertiary centre in SGPGI Lucknow (a tertiary centre in northern India), the most common causes of secondary HPP were thyrotoxicosis, RTA and Gitelman/Bartter's syndrome. ³

At Duncan Hospital in 2008, we saw patients with serum K⁺ as low as 0.8 mmol/L presenting with ventricular arrhythmias and paralysis. Recurrent hospitalizations and lack of compliance with long-term medication regimes led us to further investigate this problem. This study was designed to ascertain the common aetiological causes of HPP in northern Bihar and to develop a simple algorithm for the evaluation of HPP in secondary hospitals.

Patients/methods

The data of 84 patients was collected over a period of 3 years from February 2009 to January 2012. A standardized laboratory protocol was created in order to evaluate HPP patients. For the purposes of this study, HPP was defined as the acute loss of muscle power with limb weakness, hypo- or areflexia and a serum K⁺ value of <3.5 mmol/L.

Data collected included patient demographics, season of presentation, illness duration, prior episodes, medications, family history, and clinical examination. All patients had the following investigations: electrocardiogram (ECG); arterial blood gases (ABG); serum electrolytes; creatinine; calcium; albumin; phosphate and alkaline phosphatase; urine pH (fasting sample wherever possible); spot urine potassium and sugar. Thyroid function tests were done if clinically indicated.

The data was analysed in Microsoft Excel. STATA was used for the Spearman’s Rank coefficient for the weather data. A P value of <0.05 was considered significant.

Results

There was only a slight male preponderance in the 84 patients studied (54.8%). The largest group of patients were aged 30–39 years (38.1%).

In this study, 67 patients (79.8%) had a secondary cause for HPP with 58 having RTA (69.0%). Eight had idiopathic HPP (9.5%) and four had acute gastroenteritis (4.76%). There were two cases of probable primary hyperaldosteronism and two of familial HPP (2.38%) with one each of thyrotoxic periodic paralysis and Gitelman/Bartters syndrome (1.19% each). For eight patients, the data available was insufficient for a definite diagnosis.

The peak number of presentations annually occurs during the hottest time of the year (Figure 1). This was shown to be a significant correlation using Spearman’s Rank non-parametric test [P<0.001, 0.014 for the average maximum and minimum temperature, respectively]. ⁴ OPEN IN VIEWER

OPEN IN VIEWER

Figure 2.

A simple algorithm for diagnosing the causes of hypokalaemic periodic paralysis (HPP).

68 patients (80.9%) presented with serum K⁺< 2.0 mmol/L and 3 with serum K⁺ of ≤ 1.0 mmol/l. Two patients (2.4%) required ventilation. Recurrent episodes of HPP occurred in 30 patients (35.7%) and one had up to 10 episodes.

Discussion

We did not find the male preponderance noted in the Vellore and Lucknow series.^2,3 The previous reports may have reflected the referral bias and health-seeking behaviour of men over women in India.

Almost 80% of our patients had a secondary cause for HPP. Among the 84 patients, 58 (69.0%) had RTA. Other secondary causes were: primary hyperaldosteronism (2 patients); acute gastroenteritis (2 patients); Gitelman/Bartters syndrome (1); and thyrotoxicosis (1). These results differed from the previous clinical study at Duncan Hospital when diagnoses such as RTA may have been overlooked. ¹ Our study concurs with the causes noted in the two other Indian studies. The cases of familial HPP were identified when a girl was brought in by her father who had presented earlier in the study period.

One third of patients (35.7%) had more than one episode of HPP. The high percentage of those with an underlying cause for HPP, along with the high recurrence rates, emphasizes the need for a thorough investigation of patients with HPP. This must be coupled with patient counselling on the duration of the treatment.

The seasonal variation in HPP has not been noted in other published case series. The cause for the higher incidence in summer remains unclear. Patients with RTA are known to have an ADH resistant polyuria and, with increased dehydration in summer, the large consumption of sweetened drinks might be related to acute episodes.

Patients with severe hypokalaemia (serum K⁺ <2.0 mmol/L) and/or profound muscle weakness were given intravenous potassium chloride (KCl). Patients who were slow to improve were additionally given intravenous magnesium sulphate (MgSO₄), as hypomagnesaemia is known to produce refractory hypokalaemia. As secondary causes were identified, long-term prophylactic treatments were initiated according to the available facilities and patient finances.

A simple algorithm was developed based on our experience in the diagnosis of secondary causes of HPP in view of the limited laboratory facilities likely to be available at a secondary level hospital (Figure 2).

Conclusion

80% of the patients presenting with HPP had secondary causes, making it four times more common than primary HPP. This warrants detailed evaluation of all patients in our region with HPP in order to discover an underlying cause. RTA is the most common secondary cause of HPP in northern Bihar. Recurrent presentations highlights the need for a detailed evaluation of the first episode. Patient education about the nature of their illness is critical in order to improve compliance.

A simple algorithm was developed for use in secondary hospitals in order to assist in the aetiological evaluation. This can be used within their available facilities (Figure 2) and can be used as a tool to improve the diagnosis and management of HPP. Further investigation is needed in order to determine the extent of this problem across India and other parts of the Indian subcontinent.^5–7