Update on management of the acute abdomen in critically ill patients

 

From a recent review in Current Opinion in Critical Care Medicine:

Purpose of review

The aim of this study was to describe important features of clinical examination for the surgical abdomen, relevant investigations, and acute management of common surgical problems in the critically ill.

Recent findings

Lactate remains a relatively nonspecific marker of gut ischemia. Dual energy computed tomography (DECT) scan can improve diagnosis of bowel ischemia. Further evidence supports intravenous contrast during CT scan in critically ill patients with acute kidney injury. Outcomes for acute mesenteric ischemia have failed to improve over time; however, increasing use of endovascular approaches, including catheter-directed thrombolysis, may decrease need for laparotomy in the appropriate patient. Nonocclusive mesenteric ischemia remains a challenging diagnostic and management dilemma. Acalculous cholecystitis is managed with a percutaneous cholecystostomy and is unlikely to require interval cholecystectomy. Surgeon comfort with intervention based on point-of-care ultrasound for biliary disease is variable. Mortality for toxic megacolon is decreasing.

Summary

Physical examination remains an integral part of the evaluation of the surgical abdomen. Interpreting laboratory investigations in context and appropriate imaging improves diagnostic ability; intravenous contrast should not be withheld for critically ill patients with acute kidney injury. Surgical intervention should not be delayed for the patient in extremis. The intensivist and surgeon should remain in close communication to optimize care.

The fight to curb antimicrobial resistance: how are we doing?

 

From a recent NEJM review on this topic:

In November 2019, the CDC released an updated version of its antibiotic-resistance report…

The new report reveals reductions in the incidence of infections caused by carbapenem-resistant acinetobacter species, multidrug-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus, and drug-resistant candida species. In addition, it identifies an increasing incidence of Enterobacterales that produce extended-spectrum beta-lactamase and drug-resistant Neisseria gonorrhoeae infections and the emergence of the multidrug-resistant yeast Candida auris.

Primary aldosteronism: an update

 

Here's an update on this topic recently published in Cardiology in Review.

The original Conn syndrome was described in 1956 as a case report of a young woman with hypertension and severe hypokalemia who was found to have an adrenal adenoma and was cured after adrenalectomy. Subsequently we've found that primary aldosteronism is much more common than previously thought. It's certainly not a rare cause of secondary hypertension but it is markedly under-diagnosed.

The mechanism of action of aldosterone is described in the paper thusly:

Aldosterone, which is synthesized in the adrenal zona glomerulosa, acts primarily at the renal collecting tubule where it binds to mineralocorticoid receptors leading to an increased number of open epithelial sodium channels (ENaC) in the luminal membrane4 and increased Na-K-ATPase expression.5 Reabsorbed sodium leaves the luminal cell via the Na-K-ATPase pump. Subsequent intraluminal electronegativity triggers potassium secretion through membrane potassium channels. Additionally, aldosterone has been found to act at the second part of the distal convoluted tubule, where both the thiazide-sensitive sodium chloride cotransporter and ENaC are expressed. By regulating the function of these transporters, aldosterone is thought to have effects on sodium and chloride balance and blood pressure (BP) control.6

Hypokalemia is characteristic but only a minority of patients exhibit it at presentation.

Regarding the different etiologies, again, from the paper:

The most common cause of primary hyperaldosteronism is bilateral idiopathic hyperplasia (IHA), accounting for 60% of cases. An aldosterone-producing adenoma (APA) is seen in 30%, primary (unilateral) adrenal hyperplasia in 2%, aldosterone-producing adrenocortical carcinoma in less than 1%, familial hyperaldosteronism (FH) type 1 (glucocorticoid-remediable) in less than 1%, FH type 2 (APA or IHA) in less than 6%, and FH type 3 (germline KCNJ5 mutations) in less than 1%.9 Although germline mutations of KCNJ5 are quite rare, causing FH type 3 PA, somatic mutations of KCNJ5 are relatively common, and in one study was seen in 38% of patients with APA. These mutations are believed to increase expression of CYP11B2, the aldosterone synthase gene.10Glucocorticoid-remediable aldosteronism, which is inherited as an autosomal dominant trait, usually presents in childhood with moderate to severe hypertension. The pathophysiology involves ectopically synthesized aldosterone in the zona fasciculata under adrenocorticotropin control.

Patients with primary hyperaldosteronism have a higher cardiovascular risk then do those with comparable degrees of essential hypertension. This is believed to be due to direct extrarenal damaging effects of of aldosterone such as endothelial damage and myocardial fibrosis.

The two big questions are who should be screened and how to work it up. Guidelines are fairly aggressive in their recommendations for screening. They are covered in the paper. In brief, things that should trigger a workup include severity of hypertension (levels persistently exceeding 150 / 100), resistant hypertension which could be translated to mean failure to control the hypertension on 3 drugs or essentially any patient who is on four drugs even if controlled and hypokalemia whether spontaneous or diuretic associated. Additional candidates would include those with family history, those with early onset, and those with an adrenal incidentaloma. In addition those with sleep apnea are candidates. There is a somewhat poorly understood connection between sleep apnea and hyperaldosteronism.

It has been estimated that if these criteria or fully applied around 50% of hypertensive patients in primary care would be candidates for screening. This is straight out of of the Endocrine Society guidelines. This may seem like over testing and will certainly rule out the disorder in a substantial number of patients but it is promulgated in guidelines and published recommendations due to a substantially under-diagnosed disease burden.

Diagnosis starts with simultaneous measurement of renin and aldosterone. The renin measurement can either be plasma renin activity or renin concentration. Preferably these are done in the morning, seated for 5 to 15 minutes. The patient should be potassium and sodium replete and have diuretics discontinued. Unless the aldosterone to renin ratio is very high or spontaneous hypokalemia is observed further confirmatory testing is likely to be necessary followed by testing for the etiology of hyperaldosteronism. This includes ruling out glucocorticoid responsive hyperaldosteronism. Imaging is generally required followed often by adrenal vein sampling. Once one is past the initial screening test help from an endocrinologist or hypertension specialist might be warranted.

Procalcitonin guided antibiotic treatment is beneficial in a variety of infections

From a recent report in the American Journal of Respiratory and Critical Care Medicine :

Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear.

Objectives: To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis.

Methods: In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was greater than or equal to 80% reduction in PCT levels or any PCT less than or equal to 0.5 μg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization.

Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8–13.1%; 9/125) versus 15.3% (95% CI, 10.1–22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20–0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10–22.5%; 19/125) versus 28.2% (95% CI, 21.2–36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29–0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5–7) versus 10 (range, 7–15) days (P less than  0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm.

Conclusions: In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization.

At a Glance Commentary

Scientific Knowledge on the Subject

The procalcitonin (PCT)-guided discontinuation of antibiotic therapy was demonstrated to reduce antibiotic exposure in patients with lower respiratory tract infections and/or sepsis in several randomized trials. However, the effect on the incidence of infections by resistant microorganisms has not been studied.

What This Study Adds to the Field

The PROGRESS (Procalcitonin-guided Antimicrobial Therapy to Reduce Long-Term Sequelae of Infections) trial was designed as a real-world pragmatic trial, enrolling patients with sepsis. The trial demonstrated that PCT-guided antimicrobial treatment in sepsis was effective in reducing infection-associated adverse events like infections by multidrug-resistant organisms and Clostridioides difficile, as well as in-hospital and 28-day mortality. Generated evidence implicates that PCT guidance in sepsis is a safe strategy with long-term benefits that may have a substantial impact on public health, particularly for countries with high baseline antimicrobial consumption.

Here is a related editorial in the same issue.

Since pneumonia patients were included in the study, do these results contradict the recommendations of the community acquired pneumonia guidelines? The idea that procalcitonin levels should not be measured in patients with community-acquired pneumonia is a popular misconception of the guidelines, often promulgated via institutional pathways. All the guideline says is that if clinical judgement leads to a diagnosis of pneumonia antimicrobial treatment should be initiated regardless of the initial procalcitonin result. The guideline does not preclude calcitonin guided therapy.

Is evidence based medicine the same as science based medicine?

 In its original notion, yes.   In its widespread popular distortion, no.  Harriet Hall explains.

 

 

Widespread misunderstanding of hypoxemia, hypoxia and pulse oximetry

 

A recent article in the American Journal of Respiratory and Critical Care Medicine about hypoxemia and covid-19 concludes with this:

In conclusion, COVID-19 has engendered many surprises, but features that baffle physicians are less strange when contemplated through the lens of long-established principles of respiratory physiology.  

Read this paper when you're well rested and well fed and you will find it a great exercise in the physiology of hypoxemia. It's much more about that, and the misconceptions derived from our current obsession with pulse oximetry, than it is about covid.

First let's list what I think are some of the main ideas in the paper.

There was widespread over-reliance and misunderstanding of pulse oximetry.

There is not a simple correlation between dyspnea and hypoxemia.

The threat of hypoxemia is poorly understood by clinicians.

The seeming paradox of asymptomatic hypoxemia is not unique to covid-19 but is explained by well established principles of respiratory physiology.

Dyspnea is mediated by hypercapnia,  afferent signals produced by inflammatory stimuli, mechanical properties of the lungs and, least of all, hypoxemia.  As will be brought out in the physiology below, multiple  conditions seem to have a permissive effect on the dyspnea produced by hypoxemia.

Hypercapnia is a very important cause of dyspnea.   It has a permissive effect on hypoxemia as a cause of dyspnea. Hypercapnia causes a drop in pH in the blood perfusing the CNS respiratory control center.  An acute increase in pCO2 of 10 mm Hg quickly causes profound dyspnea. The situation is different for hypoxemia.  As pO2 falls there appears to be a threshold of 60 mm Hg  below which stimulation of ventilation and dyspnea occur. (The so called hypoxic drive). In terms of mechanism, hypoxemia stimulates the carotid bodies which send messages to the respiratory control center. From there impulses are relayed to the cortex cruising the sensation of dyspnea. The correlation between dyspnea and the ventilatory response to hypoxemia is poor. This response to hypoxemia is blunted if the pCO2 is 39 or below.  These responses are blunted in individuals with diabetes and individuals over 65 which constitute a high portion patients presenting clinically with covid.

Could covid have effects on the brain that blunt the dyspnea response? A similar question has been asked regarding the symptom of anosmia. ACE2, the receptor for covid-19, is expressed both in the carotid bodies and the nasal mucosa so mucosal effects rather than brain involvement could account for these manifestations. This is a question yet to be answered.

The authors imply that our usual concerns about low pulse oximeter  readings are misdirected.  Another quote from the article:

Physicians are fearful of hypoxemia, and many view saturations between 80% and 85% as life threatening. We served as volunteers in an experiment probing the effect of hypoxemia on breathing patterns; our pulse oximeter displayed an SpO2 of 80% for over an hour, and we were not able to sense differences between an SpO2 of 80% and an SpO2 of 90% (24). In investigations on control of breathing and oximeter accuracy, subjects experience an SpO2 of 75% (12), or briefly 45% (25), without serious harm. Tourists on drives to the top of Mount Evans near Denver experience oxygen saturations of 65% for prolonged periods; many are comfortable, whereas some sense dyspnea (25).

The finding of a low pulse oximetry reading does not enable a complete physiological assessment. Instead it should lead the clinician to ask: what's going on? Pitfalls in the interpretation of pulse oximetry were cited in the article. Correlation with blood gas readings deteriorates at lower levels of saturation. Accuracy of pulse oximetry is less in critically ill patients than in normal volunteers. The oxyhemoglobin dissociation curve should factor into any interpretation of pulse oximetry readings but this is seldom the topic of bedside discussions. Fever and low pH, common in critically ill patients, cause a shift of the curve to the right. This leads to lower saturation readings at a given pO2. It is an adaptive mechanism by which hemoglobin unloads oxygen more readily. Herein lies another reason why oxygen saturation correlates poorly with dyspnea: the carotid bodies respond to changes in pO2 but  not to oxygen saturation.

Further complicating the discussion is the definition of terms. Though not addressed in the article, there is the common confusion between hypoxemia and hypoxia. Low pO2 or saturation readings indicate hypoxemia. However, to diagnose hypoxia, which is a reduction in oxygen delivery to the tissues, one must apply the oxygen delivery equation. This equation takes into account hemoglobin bound oxygen, oxygen dissolved in plasma, hemoglobin concentration and cardiac output. As to  the definition of hypoxemia the authors point out that it has been an evolving concept. The definition of hypoxemia is not essential, but rather a matter of usage and convention. For example, in the 1990s it was often defined as the raw number without regard to the FiO2. Recently hypoxemia is more often referred to in terms of the oxygen requirement. Both are important: the former for estimating oxygen delivery and the latter for making an assessment of ventilation and gas exchange.

After reading this article I have the following concluding thoughts:

We over rely on pulse oximetry. Blood gases are underutilized.

Misunderstanding of pulse oximetry readings is widespread.

The hypoxemia of covid-19 is not as unique as popularly believed.