The following review was published in the American Journal of Kidney Diseases.
Mixed Acid-Base Disturbances: Core Curriculum 2025
This is an open access full text review. It would be difficult to reduce it down to key points. It should be read in its entirety.
This topic was recently reviewed in the article linked here:
Acute upper gastrointestinal bleeding: state of the art review
Some key points follow.
Prevention
In critical illness, PPI therapy is recommended in selected high-risk patients.
Determinants of high risk were not specified in the review.
The review recommends outpatient PPI therapy for “high risk“ patients on DAP
or oral anticoagulants without specifying the risk factors.
Acute management
For patients with hemodynamic instability, a 500 mL crystalloid bolus is recommended
for initial volume management. Specific recommendations for continued volume
management were not given, but it can be implied that subsequent bolus therapies
and running IV fluids would be based on the patient's response and clinical judgment.
Transfusion threshold
A hemoglobin target of 7 g/dl is recommended as the threshold in general. A higher
threshold may be considered in ischemic heart disease or if there is active
exsanguination. The particulars regarding those conditions were not given.
New developments in risk assessment
Artificial intelligence based risk prediction and blood sensing capsules are promising
but not ready for prime time.
Management of antithrombotics
For patients on dual antiplatelet therapy with acute bleeding, the review recommends
temporary stoppage, except for continuation of aspirin when possible if the DAP was
given for maintenance of stent patency. In such cases, the other agent should be restarted
within 5 days if bleeding is controlled.
For patients on systemic anticoagulation, mere stoppage is indicated if there is
hemodynamic stability. If unstable, reversal is indicated.
Idarucizumab is recommended for reversal of dabigatran. For patients on anti-X a
agents, andexanet or four factor PCC is recommended.
Restart of systemic anticoagulants in patients with low thrombotic risk is recommended
at 7 days or later. For high thrombotic risk, restart is recommended within 3 days,
with bridging where applicable.
Tranexamic acid is generally not recommended.
Proton pump inhibitors
The literature regarding their use is somewhat controversial, but the review
acknowledges the common practice of giving an 80 mg bolus of pantoprazole followed
by an 8 mg per hour drip or an 80 mg bolus followed by 40 mg IV BID thereafter
EGD
For all GI bleeds, at 12 to 24 hours. If variceal is suspected, less than or equal to 12
hours.
Endotrachael intubation for EGD is not routinely recommended. The recommendation for
intubation applies only to patients who are obtunded, have massive hematimesis, or
evidence of poor airway protection.
In cases of rebleeding the following sequence is recommended: repeat
endoscopy ---> IR embolizqation ---> surgery.
Special considerations in variceal bleeding:
In general, many of the recommendations for non-variceal acute upper GI bleeding apply,
but there are some special considerations. The following points regarding variceal
bleeding are drawn from guidelines published in Hepatology linked here.
AASLD Practice Guidance on risk stratification and management of portal hypertension
Cirrhotic patients with upper GI bleeding should be treated as variceal until proven
otherwise.
Such patients should be started on vasoactive therapy (eg octreotide) and intravenous
antibiotic therapy immediately. Antibiotic therapy duration is to discharge or five days,
whichever is shorter.
RBC transfusion thresholds are similar to the recommendations above for GI bleeding
in general.
EGD within 12 hours is recommended for suspected variceal bleeding.
Early TIPS (same admission) is recommended in the following patients:
Those with a CTP score greater than 7 plus active bleeding at EGD.
Any patient with CTP greater than or equal to 10 regardless of whether active
bleeding is present.
Any patient who rebleeds or whose bleeding cannot be controlled endoscopically
If TIPS is not done, non-selective beta blocker administration is recommended.
Feeding is recommended once bleeding is controlled. The presence of varices or
bands is not a contraindication to feeding per os or via tube if indicated.
Dealing with coagulation parameters in cirrhosis:
The review, the guideline, and Up to Date are vague in this area. These
recommendations are best summarized as follows:
Generally, coagulation parameters need not (and should not) be corrected.
However, room is left for clinical judgment. (If it is a nonvariceal bleed,
Up to date recommends a platelet transfusion target of 50K).
Cryoprecipitate, either empirically (in active bleeding) or if fibrinogen is below
120K is stated to be “reasonable“ by the Up to Date authors. (The Up to Date
article is vague as to whether this recommendation applies to variceal bleeding,
non-variceal bleeding or both).
Thus, there is considerable room for clinical judgment. The underlying rationale
for the recommendations regarding coagulation management in cirrhosis is as follows:
Portal pressure, not hemostasis, is the principal driver of bleeding.
Due to the ”rebalanced hemostasis” characteristic of cirrhosis, coagulation parameters
are not predictive of bleeding risk.
The volume load of FFP needed to ”correct” an elevated INR will likely increase
portal pressure, thus aggravating bleeding.
There's insufficient evidence regarding 4 factor PCC in cirrhotic bleeding. In
general, it is not recommended unless for anticoagulant reversal.
This topic was reviewed in an article in the February 2024 issue of the American Journal of Medicine, linked here:
The Safe Use of Analgesics in Patients with Cirrhosis: A Narrative Review
Here are key points regarding various categories of analgesics:
Acetaminophen
Contrary to prevailing myth, acetaminophen is safe in patients with liver disease, including cirrhosis, provided dose limitations are applied.
In patients with liver disease who are actively consuming ethanol, short-term use up to two grams per day is permissible. For chronic use in patients not actively consuming alcohol a limit of two grams per day is also advised. Up to four grams per day may be permissible in cirrhotic patients not consuming alcohol for short-term use
NSAIDs
Systemic use is contraindicated for a variety of reasons. Topical diclofenac appears safe.
Opiates
In general, opiate use in patients with cirrhosis is associated with increased rates of hospital admission, increased length of stay, and an increased incidence of hepatic encephalopathy.
According to the review, they should be limited to short-term use and confined to short-acting preparations.
Gabapentin and pregabalin
These agents undergo virtually no hepatic metabolism and are considered safe in cirrhosis. Of course, like any drug with sedative effects, there is the potential to precipitate hepatic encephalopathy.
Duloxetine
This is widely used in pain treatment. However, adverse hepatic outcomes have been reported and it is considered contraindicated in liver disease. This recommendation is in keeping with product labeling.
Topical lidocaine is considered safe.
A recent review of the topic appeared in Lancet Infectious Disease, linked here:
Tetanus: recognition and management
General
Tetanus is rare in the developed world but worth discussing because it is a must not miss diagnosis.
Tetanus is caused by infection with Clostridium tetani. It produces a neurotoxin that is transported to the CNS retrogradely (by reverse axonal transport) where it blocks inhibitory neurotransmitter release thereby allowing unopposed motor activity. Four forms of tetanus are described: neonatal (not discussed here), localized (near the site of injury), cephalic (localized to the head and neck ), and generalized. Either of the localized forms can progress to generalized tetanus.
Epidemiology
Although considered rare in the developed world, 17 to 33 cases are diagnosed yearly in the United States. Inoculation sources can include any violation of skin integrity. Injection drug use, any type of wound, piercings, acupuncture, subQ or IM injections (either therapeutic or recreational), are possible sources. Up to 30% of cases are associated with no discernible history of a wound or injury. This epidemiology argues strongly for universal vaccination.
Clinical features
Clinical features include rigidity, spasm, trismus, opisthotonus, and dysphagia. Fever is often present but not invariably at presentation.
Diagnosis
Diagnosis is based on clinical features and confirmatory testing. A high index of suspicion is important due to non-textbook presentations (acute abdomen, dysphagia, stroke concerns, dystonia). The diagnostic test of choice is C tetani PCR from wound material. Anti tetanus toxin antibodies are also recommended, and while a low tighter is supportive of the diagnosis and high antibody levels rule against the diagnosis, this test is not definitive. Occasional cases have been reported in patients who had “protective” antibody titers.
Aspects of immunity
Natural infection does not confer immunity. Near elimination of the disease in the developed world is attributable to universal vaccination practices. Since there is no person to person transmission, herd immunity does not exist.
Treatment
Surgical debridement even for innocuous appearing wounds is indicated. Antibiotics should include metronidazole which according to low level evidence is associated with better overall outcomes. Antioxin in the form of tetanus immunoglobulin is indicated. Invasive mechanical ventilation is necessary in around 50% of patients and should this be required, primary tracheostomy is preferred.
Benzodiazepines are an important part of the treatment with diazepam as the benzo of choice. High doses and continuous drips are often necessary. Adjunctive neuromuscular blockade may be needed.
Dysautonomia
Dysautonomia is common and is a significant cause of mortality.
IV magnesium sulfate as a treatment for dysautonomia is associated with improved outcomes and a bolus/drip regimen is recommended, targeting serum levels of 2 to 4 mmole/L. Opiates have a significant role in the management of dysautonomia. Otherwise, vasoactive drugs as appropriate for the patient’s hemodynamic state may be indicated.
Finally, general symptomatic and supportive care to include fluids, nutritional support, stress ulcer prophylaxis, VTE prophylaxis along with skin and wound care are indicated.
