International Journal of Academic Medicine

: 2015  |  Volume : 1  |  Issue : 1  |  Page : 21--26

Scrutinizing the evidence linking hypokalemia and ileus: A commentary on fact and dogma

William Matthew Brigode1, Christian Jones2, Daniel E Vazquez2, David C Evans2,  
1 Department of General Surgery, University of Illinois at Mt. Sinai Hospital, Columbus, USA
2 Department of Surgery, Division of Trauma, Critical Care, and Burn, Ohio State University Wexner Medical Center, Columbus, USA

Correspondence Address:
William Matthew Brigode
Department of General Surgery, University of Illinois at Mt. Sinai Hospital, 1500 South Fairfield Avenue, Chicago, Illinois 60608


Low serum potassium has been linked to classic signs and symptoms including mental status changes, muscular dysfunction and paralysis, and cardiac arrhythmias. Frequently, it has been listed as a cause for paralytic ileus, and correcting electrolyte anomalies is one of the first steps in treatment of a patient with nonfunctioning bowels. However, our review of the literature does not support a clear causative link. Older studies cite potassium as one of the many factors to optimize to regain bowl function, while newer studies do not support hypokalemia as a cause of ileus. Current treatment of ileus supports focusing on reversal of the effect of opiates on the gut, while electrolyte therapeutic goals are directed to prevent complications outside of the gastrointestinal (GI) tract. We review the cellular physiology and clinical data to elucidate the nature of the link between low potassium values and its impact on GI motility. Patients: Patients with hypokalemia and ileus. Intervention: Potassium repletion. Comparison: Patients with normal potassium values. Outcomes: Resolution of ileus. Population, intervention, comparator, and outcomes questions: Does low serum potassium cause intestinal ileus, and will correction of this deficit correct the intestinal paralysis?. The following core competencies are addressed in this article: Practice-based learning and improvement of medical knowledge. This article addresses the evidence linking hypokalemia and ileus to improve medical knowledge and enable physicians to put this evidence into practice.

How to cite this article:
Brigode WM, Jones C, Vazquez DE, Evans DC. Scrutinizing the evidence linking hypokalemia and ileus: A commentary on fact and dogma.Int J Acad Med 2015;1:21-26

How to cite this URL:
Brigode WM, Jones C, Vazquez DE, Evans DC. Scrutinizing the evidence linking hypokalemia and ileus: A commentary on fact and dogma. Int J Acad Med [serial online] 2015 [cited 2021 Jan 21 ];1:21-26
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Hypokalemia's association with surgical complications is unclear. Common teaching is to replace electrolytes according to strict guidelines after intestinal surgery, often due to the claim that hypokalemia is a cause of ileus.[1] However, data supporting this linkage are not definitive in the literature. Modern citations for the treatment of potassium deficiency specific to postsurgical patients with paralytic ileus refer to the 1971 article by Lowman of 18 patients.[2] These patients had prolonged paralytic ileus after various abdominal surgeries. The operations were mostly urologic with a few hysterectomies and bowel resections. The patients had dilated bowels and hypokalemia; correction of the hypokalemia decreased the dilation. However, he does not provide serum potassium before and after treatment in this group of patients. He cites a group of 32 other patients with radiologic intestinal distension with potassium in the range of 2.8–3.5 mmol/L. After treatment, these patients recovered, but he does not elaborate on the method, the timing, or the goal serum potassium of treatment. Finally, he recognizes that hypokalemia is not the only factor contributing to ileus in these patients.

Lowman noted further sources from the 1950s that described potassium's physiologic role in intestinal motility.[3],[4] These experiments on dogs linked the serum potassium concentration to changes in intestinal propulsion, but the main conclusion was that intracellular, but not extracellular, potassium deficiency could cause intestinal paralysis. In fact, these experiments found association between complete intestinal paralysis and a rise in serum potassium, rather than a drop. It had also previously been demonstrated that intracellular potassium deficiency was not consistently represented in serum values.[5],[6],[7] In dehydration and shock, intracellular deficiency can occur not just with low extracellular values, but with normal or high serum values.[8] Discussions within these articles suggested that potassium was not necessarily in all patients' fluid therapy; patients could have a negative potassium balance with minimal potassium intake but continued gastrointestinal (GI) and urinary losses. Thus, these patients were predisposed to whole body depletion of potassium, but the traditional serum values measured may not represent that state.

While historical data do not form a clear link, modern studies provide some insight into the relative impact of potassium management on the postoperative patient. A sample of 413 patients undergoing laparoscopic colectomy showed that age over 60, preoperative narcotic use, and previous abdominal surgery were the only three independent risk factors for the development of a postoperative ileus (POI). Patients' mean postoperative potassium and magnesium values were not significantly associated with ileus while hypocalcemia was.[9] However, each patient's lowest postoperative potassium level was highly correlated with POI (as was hemoglobin level). In this study, the POI patients had more lab draws than the nonileus group. The study suggested that the increased number of draws can unintentionally smooth the data, creating an average that shows no statistical correlation because outlier low potassium levels were replaced and rechecked, and the values after replacement were included in the results.

The study did not comment on whether this trough potassium is a cause or an effect of ileus. Also, the hypokalemia was not identified as an independent risk factor when multivariable analysis controlled for narcotic use, prior surgery, and age. The association of POI with low average postoperative calcium, lowest postoperative potassium, and lowest postoperative hemoglobin may mean these risk factors are dependent on another variable, such as a more extensive or traumatic operative dissection. Furthermore, the study is limited to minimally invasive colon surgery, which may not be generalized to all abdominal surgeries.

Many sources tend to agree that the trauma of surgery leads to a catabolic state that predisposes to potassium wasting. The nil per os (NPO) status of surgical patients limits the dietary potassium and fluid intake, while catabolism and the high aldosterone state after surgery tend to deplete the body's stores. Patients who are NPO have relative hyperglycemia and experience hyperinsulinemia with subsequent shifts of electrolytes.[10] Potassium is shifted into cells and out of the measurable extracellular space.

 Basic Science

To better understand the physiologic implications of hypokalemia, it is worthwhile to review the underpinnings of potassium regulation both in the cell and in the neurenteric system as it relates to gut motility. The human body balances the intake of dietary potassium with excretion of urinary and fecal potassium. Potassium can also be shifted within various body compartments. The intake-output balance and inter-compartmental shifts determine the concentration of the potassium ions in each compartment. The relative gradients between compartments form the driving force for neural conduction. In muscle cells, potassium gradients are linked with calcium as the basis for muscle cell contraction.

 Cellular Physiology

The normal amount of potassium in a 70 kg healthy male is approximately 3700 mmol. Each day, approximately 100 mmol are consumed and absorbed, driven passively by the concentration gradient across the intestinal mucosa. Most is excreted by the kidneys. Throughout the nephron, multiple mechanisms passively and actively absorb and secrete potassium. Under higher potassium loads, aldosterone actively mediates the increased potassium excretion, which can reach as high as 1000 mmol/day. Conversely under low potassium loads, potassium is retained down to a minimum excretion of 10 mmol/day.[11] However, the normal daily renal excretion is around 90 mmol/day with the remaining daily potassium excreted in feces at a rate of 10 mmol/day.

The balance of potassium is largely affected by its distribution and excretion as they react to intake. Many conditions pertinent to the surgical patient may alter potassium. Intracellular and extracellular potassium and hydrogen ions exchange across plasma membranes, thus linking acidosis with hyperkalemia and alkalosis with hypokalemia. Renal insufficiency may cause acute or chronic potassium retention. Low magnesium values may lead to inappropriate potassium excretion. In diarrheal states, enteric losses may increase to 80 mmol/day and far exceed the 10 mmol/day typically associated with potassium homeostasis.

The balance and regulation of potassium lead to a normal plasma and extracellular fluid concentration of 3.5–5.0 mmol/L. This accounts for only 60 mmol of body potassium; most body potassium (3300 mmol) is stored in cells. The largest contributor to cellular potassium is skeletal muscle, which has a potassium concentration of approximately 150 mmol/L. This results in a high intracellular to extracellular concentration ratio of potassium (150:4). This ratio is primarily maintained by the K +/Na + ATPase, which pumps potassium into cells in exchange for sodium. This results in a reversed intracellular to extracellular concentration ratio of approximately 10:140 for sodium. The imbalance of sodium, potassium, and other ions lead to a combined imbalance of concentration and charge. These compose the resting membrane potential that supports many physiological mechanisms from trans-cellular transport to muscular and neural function.

Neural and muscular cells have parallel functions. At a synapse, the localized release of neurotransmitters activates ligand-gated channels, allowing Na + into the cell, starting to depolarize the resting potential of the cell. This is amplified after a threshold is reached as voltage-gated Na + channels allow more Na + into the cell. Once fully depolarized, the cell becomes impermeable to Na +, but permeable to K + via voltage-gated K + channels. This allows K + out of cells, returning the polarity of the cell to its resting potential. The Na +/K + ATPase continues to maintain the gradients of the ions lost in depolarization and repolarization. The local action at a synapse triggers surrounding membranes and this propagates down the length of a neuron or muscle cell. In neurons, depolarization can lead to release of vesicular neurotransmitters able to trigger another cell.

In all muscle cells, depolarization of the gradients of Na + and K + is linked to the third ion Ca ++. At baseline, Ca ++ ATPases pump Ca ++ into the sarcoplasmic reticulum (in skeletal muscle cells) and into the extracellular fluid (ECF) (in all muscle cells). When a muscle cell is depolarized, Ca ++ is allowed back into cells via voltage-gated channels. The increased intracellular concentration of Ca ++ is then linked to the mechanisms of contraction of skeletal, cardiac, and smooth muscle cells. Also, GI smooth muscle has a ligand-gated Ca ++ receptor, allowing ligands to raise the intracellular Ca ++ concentration and trigger contraction. These ligands participate in the neurocrine and paracrine signaling in intestinal motility. Finally, smooth muscles have ion-permeable gap junctions to allow linked cells to act functionally as one. In this signaling system, Ca ++ ions are the ions mediating the action, but potassium and sodium are the primary ions causing the resting potential in all cells. When whole body potassium is altered, this sets up the potential to alter the initial Na +/K + depolarization that incites the Ca ++ depolarization that eventually contracts the cell.

 Neural Physiology of the Bowel

The intestinal innervation has various levels of control. The neurons closest to the intestinal musculature are the interstitial cells of cajal, which exist in a network of two plexuses. The Meissner (submucosal) plexus is between the mucosa and the circular muscle, while the Auerbach (myenteric) plexus lies external to the circular muscle and inside the longitudinal muscle. The neural cells of these plexuses have a physiology that parallels cardiac pacemaker cells. They are arranged in a network to coordinate slow repetitive variances in the membrane potential, known as slow waves. Below a threshold level, the slow waves do not induce action potentials and muscle contraction in the intestinal musculature. However, if the threshold is reached, the intestines will contract in coordination with each slow wave of sufficient magnitude.

Coordinated motility of the GI tract is not only dependent on the network of the cells, but the inputs mediating and controlling these reflexes. Sensory components within the tract can sense physical and chemical conditions within the tract. Local distension can mediate a reflex within the enteric nervous system (ENS). Likewise, the presence of chemical components within the tract can alter the reflexes mediating complex actions such as those required for bile and pancreatic enzyme secretion via paracrine action. These paracrine hormones exert their action through depolarizing or hyperpolarizing their target neurons, thus creating electric signals to be incorporated into the motility pattern.

The reflexes of GI motility are additionally under the influence of higher order neurons of the central autonomic nervous system (CNS). Autonomic control over the ENS is exerted by the pathways of the sympathetic and parasympathetic nerves. Sympathetic CNS control arrives via the thoracolumbar paravertebral ganglia. Parasympathetic CNS control arrives via the vagus and pelvic splanchnic nerves. The sympathetic and parasympathetic nerves coalesce in the celiac, superior, and inferior mesenteric ganglia. These nerves then exert their control on the ENS via the balance of sympathetic and parasympathetic tone. Sympathetic innervation can hyperpolarize the postsynaptic membrane, preventing depolarization and thus inhibiting the ability for slow waves to meet action potential threshold. Conversely, parasympathetic innervation can bring postsynaptic membranes closer to depolarization, accelerating activity, and contractions.

The network of cyclical slow waves in conjunction with the local reflexes and under the influence of the CNS forms patterns of muscular contraction of the GI tract. Some waves coordinate muscle to propulse GI contents forward in the lumen. Other waves are altered to desynchronize the contractions, decreasing forward propulsion and promote trituration and mixing movements within the lumen. Furthermore, the stomach and colon have coordinated activity suppression needed to promote simple storage of contents. Hypokalemia may lead to reduced neural conduction to and within the ENS, altering the normally highly coordinated reflexes and patterns of GI motility, with the result being one mechanism linking potassium levels to paralytic ileus.

 Clinical Effects of Hypokalemia

Potassium role in the resting membrane potential in motor and neural cells may explain how its depletion from the body is tied closely with neural and motor function. Each neuron within the ENS and CNS requires potassium homeostasis for optimal function. When potassium levels inside and outside of cells are disturbed from their respective normal concentrations, neuromuscular functions are abnormal. [Table 1] summarizes these abnormalities. Mild hypokalemia (<3.5 mmol/L) may be asymptomatic or linked to nonspecific symptoms such as mental status changes or muscular dysfunction.[11],[12],[13] Thus, the traditional threshold for clinical hypokalemia and treatment has been 3.5 mmol/L.{Table 1}

Further losses (<3.0 mmol/L) are linked to progressive muscular dysfunction from weakness to paralysis.[12],[13],[14] Many conditions associated with acute and chronic hypokalemia can be linked to paralysis of skeletal muscle. Treatment of the acute hypokalemia and these underlying conditions reverses the paralysis, but no data support a specific value as a treatment goal.

Potassium replacement guidelines in cardiac care have been more thoroughly researched. Hypokalemia has defined changes during cardiac depolarization phases, which translate to the electrocardiogram changes of QT prolongation, T wave flattening, and U wave development.[15] Large trials have shown that hypokalemia below 3.5 mmol/L is associated with atrial fibrillation,[16] and ventricular arrhythmias below 3.0 mmol/L.[15],[17] However, there have been no trials to determine the benefit of replacing potassium to a value of 4.0. Rather this treatment, goal is due the strong correlation linking hypokalemia to ventricular arrhythmias in patients with acute myocardial infarctions.[17] While a cutoff of 3.5 mmol/L is statistically significant, replacing to 4.0 mmol/L provides a margin of variance to avoid the dangerous range. Some cardiothoracic surgeons strive for even higher levels (e.g., 4.2–4.5 mmol/L) in chest operations with high rates of atrial fibrillation.[18]

The above data are what our review of the literature supports in terms of symptoms at various degrees of hypokalemia as well as treatment goals in certain conditions. Evidence shows nonspecific symptoms below 3.5 mmol/L, muscle paralysis below 3.0 mmol/L, and predisposition to various arrhythmias depending on the level of hypokalemia. While replacing potassium is said to correct the noncardiac symptoms, no data support an optimal potassium level outside of cardiac patients. In addition, the common clinical goal of raising potassium concentration to 4.0 mmol/L is to give a buffer against the statistical cutoff of 3.5 mmol/L.

While many sources suggest hypokalemia is associated with ileus, our review of the literature only found the historical sources detailed above. These are based on experiments in dogs that have unclear conclusions. The human subjects in the subsequent studies had mild hypokalemia (2.8–3.5 mmol/L). However, they did not give data to support a correlation of the hypokalemia with ileus, and they did not have data to support a corrected goal that resolved the patients' symptoms.

 Treatment of Postoperative Ileus

Being dogmatic, the treatment of POI varies institution to institution and physician to physician. However, many common tenets involve keeping the patient NPO, providing nasogastric decompression when indicated, providing maintenance fluids, minimizing narcotics, and optimizing electrolytes. The only intervention with evidence in the literature is for the limited use of narcotics and reversal of opiate action on mu-receptors of the gut.[19] This treatment appears to be effective without significant attention to potassium levels.[20] Potassium supplementation is frequently the core ion in question when optimizing electrolytes, but the aforementioned evidence does not associate postoperative potassium levels with POI. Given the other dangers of hypokalemia, there have been no trials specifically addressing the effect of potassium supplementation versus withholding supplementation. A look at the cardiac evidence of symptomatology at suboptimal potassium levels sheds light on the dogmatic goals of potassium supplementation. Permissive hypokalemia would not be clinically ideal given the cardiac risks, but our evaluation of the evidence would caution against depending on potassium supplementation as a means to resolving paralytic ileus.


Potassium plays a vital role in cellular physiology. Appropriate concentrations in intracellular and extracellular fluids are required for proper maintenance of resting membrane potentials and progression of normal action potentials. Hypokalemia has been described as associated with nonspecific symptoms such as weakness and mild mental status changes, while more severe deficits may result in cardiac arrhythmias, muscle paralysis, or paralytic ileus.

Reassessing research on the association between hypokalemia (specifically low serum potassium concentrations) and ileus shows an unclear relationship. Older case histories and small, undefined population have been presented reporting potassium repletion associated with the resumption of bowel function. One modern study has demonstrated an association between low trough potassium levels with POI, but this association was not independent on multivariable analysis. No studies show a clear mechanism defining whether serum hypokalemia is a cause of POI or vice versa. Indeed, older laboratory data support a deficiency of intracellular potassium as a cause of intestinal paralysis and recognizes a poor correlation between serum, intracellular, and total body potassium. Current pharmacologic treatment of POI focuses on reversal of opiate action on mu-receptors of the gut, which appears to be effective without significant attention to potassium levels. Abnormal potassium levels are associated with a plethora of potential complications, including dangerous arrhythmias. As such, while inattention to potassium levels is inappropriate, considering routine potassium replacement, a key to preventing POI, is likely inappropriate as well.

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Conflicts of interest

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