Aly MK (2021) Acute Delirium and Difficult Sedation Weaning in ICU Thiamine Deficiency Maybe a Possible not Uncommon Cause. Int J Crit Care Emerg Med 7:131.

Case Report | Open Access DOI: 10.23937/2474-3674/1510131

Acute Delirium and Difficult Sedation Weaning in ICU Thiamine Deficiency Maybe a Possible not Uncommon Cause

Magdy Khames Aly, Ms*

Critical Care Medicine, MRCP, United Arab Emirates


This is a case of 54-years-old critically ill H1N1 ARDS patient with prolonged ventilation and sedation and difficult weaning from sedation and mechanical ventilation. The case gives spotlight on not uncommon cause of delirium and failure of weaning in critically ill patients which is Vitamin B1 deficiency and how it is underestimated and should be put in mind while management those patients.


Acute delirium, Acute confusion state, Thiamine deficiency, Encephalopathy, Sedation weaning, Ventilator weaning, ICU, Critically ill


Thiamine is a water-soluble vitamin that is absorbed in the jejunum by 2 processes. When the thiamine level in the small intestines is low, an active transport portal is responsible for absorption. When the thiamine concentration is high, a passive mucosal process takes place. Up to 5 mg of thiamine is absorbed through the small intestines. The small intestine is where phosphorylation of thiamine takes place [1,2].

The body cannot produce thiamine and can only store up to 30 mg of it in tissues. Thiamine is mostly concentrated in the skeletal muscles. Other organs in which it is found are the brain, heart, liver, and kidneys. The half-life of thiamine is 9-18 days. It is excreted by the kidney [3,4].

Persons may become deficient in thiamine by not ingesting enough vitamin B-1 through the diet or may become deficient through excess use; the latter may result from hyperthyroidism, pregnancy, lactation, or fever. Prolonged diarrhea may impair the body's ability to absorb vitamin B-1, and severe liver disease impairs its use [5,6].

Causes of Thiamine Deficiency in Critically Ill Patients

Increased consumption states [5-8]

• Increased metabolic consumption of thiamine can result from the following:

• Diets high in carbohydrate or saturated fat intake

• Hyperthyroidism

• Fever - Severe infection/sepsis

• Refeeding syndrome (carbohydrate metabolism is increased)

Increased depletion [9-11]

Increased thiamine depletion can result from the following:

• Diarrhea

• Diuretic therapies

• Peritoneal dialysis

• Hemodialysis/continuous renal replacement therapy

Decreased absorption [12,13]

The following factors can result in decreased thiamine absorption:

• Chronic intestinal disease

• Alcoholism

• Malnutrition

• Gastric bypass surgery

• Malabsorption syndrome - Celiac and tropical sprue

• Folate deficiency - For example, in patients undergoing chemotherapy with high-dose methotrexate

• Drug-vitamin interaction can prevent intestinal absorption of thiamine causing deficiency

Lack of thiamine intake [6,7,12,13]

The following diet-related factors can also cause reduced thiamine intake:

• Alcoholic state

• Starvation state

• Gastric bypass surgery - Due to limited caloric intake during postsurgical repair (approximately 600-900 kcal/day)

• Parental nutrition without adequate thiamine supplementation

Delirium is a common manifestation of acute brain dysfunction in critically ill patients that is associated with poor short-term outcomes and may result in adverse sequelae years after ICU discharge. The strategies described for the prevention, diagnosis, and treatment of ICU delirium is subjects of multiple ongoing investigations. Every ICU clinician should be aware of these strategies, institute routine monitoring for delirium in the ICU, seek to reduce the impact of risk factors for delirium when possible, and use treatment options when necessary [14-16].

Thiamine deficiency maybe the cause in many situations in critically ill patients causing delirium and sedation dependent and difficult weaning from sedation and mechanical ventilation. Other medical conditions such as stroke, drug overdose, other encephalopathy, and infections such as meningitis could mimic WE. These disorders should be thoroughly evaluated, particularly in patients at low risk for WE [17].

Conversely, WE can be precipitated in high-risk patients such as those with critical illness or sepsis due to increased metabolic demand causing relative thiamine deficiency. In patients with cancer, absolute thiamine deficiency can occur because of malabsorption, malnutrition, or vomiting, triggering WE [18-21].

In this case report we can find how thiamine supplementation helped the patient to wean from sedation and MV and improves the delirium state.

Case Report

A 54-year-old male patient admitted to the ICU on 21/01/2020 with the history begun over the previous 10 days by fever, nausea, vomiting and dry cough, initially admitted to HDU on 18/01/2020 by SOB, dry cough requiring NC 2 L/minute which gave him SATO2 of 95-96% but the patient progressively deteriorating over the following 2 days with increasing respiratory distress, desaturation, increasing O2 requirements upgraded to NR mask with high flow and then NIV, XR Chest showed bilateral patchy lung fields with obliteration of cardiopulmonary angle, ABG with mild hypoxia and respiratory alkalosis. However, the patient continued deterioration on 21/01/2020 morning Patient SATO2 decreased to 80% with severe tachypnea so intubation and Mechanical Ventilation started. Bronchoscopy done on 21/01/2020 and BAL sample has been PCR tested confirmed H1N1 ARDS lung pneumonia. Patient has been put on sedation including Midazolam, Fentanyl, Propofol and paralytic agent was add also to control ventilation with high FIO2 requirement and PEEP, Tazocin, Tamflu, Levofloxacin have been given and Meropenem and Linezolid add later in ICU day 8.

ICU day 12 patient maintaining SATO2 94-95% on SIMV PC 14 PEEP 14 FIO2 50%.

On 31/01/2020 patient requiring more sedation to synchronize with MV so sedation increased to Fentanyl 150 mcg, midazolam 5 mg, Precedex 1 mcg/kg/hr and Propofol 100 mg.

On 01/02/2020 Fentanyl decreased to 80mcg, midazolam decreased to 4 mg, propofol off, Precedex remain the same, Seroquel 25 mg TID added.

From 01/02 to 10/02 patient improved as regard ARDS on PEEP 7, FIO2 40% but still deeply sedated and showed failure of weaning from sedation, patient became distressed, tachycardiaic, desaturation after one hour from just decreasing the sedation or making sedation vacation.

Seroquel dose increased to 50 mg TID and Clonidine added to help for weaning from sedation but unfortunately could not wean from sedation at all with hyperactive delirium.

From 11/02 to 29/02 tracheostomy was done but the patient showed failure from weaning from sedation with suffering from hyperactive delirium and agitation.

On 02/03/2020 LP was done as recommendation from neurologist to diagnose the cause for agitation with provisional diagnosis of post viral encephalopathy or viral encephalitis but the analysis returned normal.

ICU team decided to give Thiamine 100 mg daily for 3 days as a provisional diagnosis of Wernicke's encephalopathy, the patient showed dramatic improvement after 2 doses as regard the weaning from sedation and successfully weaned off from sedation and also from MV completely and became stable on T-piece.

Patient then discharged from the ICU to the medical ward after 10 days after tracheostomy decannulation on only NC 2 L/minute.


It is obvious from this case that the frequently faced problem of ICU delirium can be caused by thiamine deficiency which in turn frequently underestimated.

ICU delirium frequently happened in critically ill patients for many etiologies like sedative-related delirium, Postanesthesia delirium, critical illness delirium caused by hypoxia, sepsis, drug induced.

Assessment of delirium in ICU is very important to decrease the morbidity and mortality and to decrease ICU stay time. Many tools of assessment used to diagnose delirium Confusion Assessment Method for the ICU (CAM-ICU), Intensive Care Delirium Screening Checklist (ICDSC), Richmond Agitation-Sedation Scale (RASS) [22-31].


The Best Treatment of Delirium is Prevention; Early Mobilization is the Most Important Measure.

The ABCDEF bundle refers to A for Assess, Prevent, and Manage Pain: prevention of agitation and delirium by adjusting the type and dose of analgesic drugs based on the assessment of patients' pain levels; B for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials: daily interruption of sedative and analgesic infusions until the patient is awake and can follow instructions, or until the patient feels uncomfortable or agitated, and it is believed that the sedation therapy should be restarted; C for Choice of Analgesia and Sedation: light sedation does not mean inadequate sedation, deep sedation does not mean excessive sedation, sedation assessment means assessment of agitation and sedation, goal-directed sedation and analgesia based on sedation can reduce the severity and duration of delirium, and prevent delirium; D for Delirium: Assess, Prevent, and Manage: Daily delirium assessment and constant monitoring of delirium when RASS scores fluctuate is an important measure for the management of delirium; E for Early Mobility and Exercise; and F for Family Engagement and Empowerment: Both E and F can promote the recovery of patients and prevent delirium and shorten its duration [32-37].

In our case ABCDEF bundle used but the patient persistently delirious, with dependence on sedatives with very difficult weaning from sedations and MV.

So we thought about Wernicke's encephalopathy and Thiamine deficiency specially the patient received loop diuretics during his stay in the ICU which is one of the causes of deficiency as mentioned before.


-Thiamine deficiency in critically ill patient is not uncommon.

-Thiamine deficiency should be considered as one of the causes of ICU delirium.

-Thiamine should be given empirically in ICU patient, it can help.


  1. Wiley KD, Gupta M (2020) Vitamin B1 Thiamine Deficiency (Beriberi). StatPearls.
  2. Wooley JA (2008) Characteristics of thiamin and its relevance to the management of heart failure. Nutr Clin Pract 23: 487-493.
  3. Isselbacher KJ, Braunwald E, Wilson JD (1994) Harrison’s principles of internal medicine. (13th edn), McGraw-Hill, New York, NY, 474-475.
  4. McCormick DB, Shils ME, Young VR (1988) Modern nutrition in health and disease. Lea and Febiger, 355-361.
  5. Masumoto K, Esumi G, Teshiba R, Nagata K, Nakatsuji T, et al. (2009) Need for thiamine in peripheral parenteral nutrition after abdominal surgery in children. JPEN J Parenter Enteral Nutr 33: 417-422.
  6. Matrana MR, Davis WE (2009) Vitamin deficiency after gastric bypass surgery: A review. South Med J 102: 1025-1031.
  7. Ahmed A, Daida Y, Novotny R (2011) PS2-02: Micronutrient Deficiencies After Bariatric Surgery: Does Ethnicity Matter?. Clin Med Res 9: 165.
  8. Francini-Pesenti F, Brocadello F, Manara R, Santelli L, Laroni A, et al. (2009) Wernicke's syndrome during parenteral feeding: Not an unusual complication. Nutrition 25: 142-146.
  9. Al-Attas OS, Al-Daghri NM, Alfadda A, Abd Al-Rahman SH, Sabico S (2011) Blood thiamine and derivatives as measured by high-performance liquid chromatography: Levels and associations in DM patients with varying degrees of microalbuminuria. J Endocrinol Invest 35: 951-956.
  10. Wiesen P, Van Overmeire L, Delanaye P, Dubois B, Preiser JC (2011) Nutrition disorders during acute renal failure and renal replacement therapy. J Parenter Enteral Nutr 35: 217-222.
  11. Sica DA (2007) Loop diuretic therapy, thiamine balance, and heart failure. Congest Heart Fail 13: 244-247.
  12. Braverman LE, Utiger RD (1996) Werner and Ingbar’s the thyroid: A fundamental and clinical text. (7th edn), Lippincott Williams & Wilkins, Baltimore, Md, 694, 864.
  13. Sriram K, Manzanares W, Joseph K (2012) Thiamine in nutrition therapy. Nutr Clin Pract 27: 41-50.
  14. Ely EW, Gautam S, Margolin R, Francis J, May L, et al. (2001) The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med 27: 1892-1900.
  15. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, et al. (2004) Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 291: 1753-1762.
  16. Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW (2004) The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev 14: 87-98.
  17. Donnino MW, Vega J, Miller J, Walsh M (2007) Myths and misconceptions of Wernicke’s encephalopathy: What every emergency physician should know. Ann Emerg Med 50: 715-721.
  18. Charness ME, DeLaPaz RL (1987) Mamillary body atrophy in Wernicke’s encephalopathy: antemortem identification using magnetic resonance imaging. Ann Neurol 22: 595-600.
  19. Harper CG, Giles M, Finlay-Jones R (1986) Clinical signs in the Wernicke-Korsakoff complex: A retrospective analysis of 131 cases diagnosed at necropsy. J Neurol Neurosurg Psychiatry 49: 341-345.
  20. Victor M, Adams RD, Collins GH (1989) The Wernicke-Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition. (2nd edn), FA Davis, Philadelphia, PA.
  21. Isenberg-Grzeda E, Shen MJ, Alici Y, Wills J, Nelson C, et al. (2017) High rate of thiamine deficiency among inpatients with cancer referred for psychiatric consultation: Results of a single site prevalence study. Psychooncology 26: 1384-1389.
  22. Cerejeira J, Firmino H, Vaz-Serra A, Mukaetova-Ladinska EB (2010) The neuroinflammatory hypothesis of delirium. Acta Neuropathol 119: 737-754.
  23. Sharshar T, Carlier R, Bernard F, Guidoux C, Brouland JP, et al. (2007) Brain lesions in septic shock: A magnetic resonance imaging study. Intensive Care Med 33: 798-806.
  24. Barr J, Egan TD, Sandoval NF, Zomorodi K, Cohane C, et al. (2001) Propofol dosing regimens for ICU sedation based upon an integrated pharmacokinetic-pharmacodynamic model. Anesthesiology 95: 324-333.
  25. Brummel NE, Ely EW (2014) Sedation level and the prevalence of delirium. Intensive Care Med 40: 135.
  26. Golinger RC, Peet T, Tune LE (1987) Association of elevated plasma anticholinergic activity with delirium in surgical patients. Am J Psychiatry 144: 1218-1220.
  27. Chang YL, Tsai YF, Lin PJ, Chen MC, Liu CY (2008) Prevalence and risk factors for postoperative delirium in a cardiovascular Intensive Care Unit. Am J Crit Care 17: 567-575.
  28. Patel SB, Poston JT, Pohlman A, Hall JB, Kress JP (2014) Rapidly reversible, sedation-related delirium versus persistent delirium in the Intensive Care Unit. Am J Respir Crit Care Med 189: 658-665.
  29. Kress JP, Pohlman AS, O’Connor MF, Hall JB (2000) Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 342: 1471-1477.
  30. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, et al. (2008) Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in Intensive Care (Awakening and breathing controlled trial): A randomised controlled trial. Lancet 371: 126-134.
  31. Haenggi M, Blum S, Brechbuehl R, Brunello A, Jakob SM, et al. (2013) Effect of sedation level on the prevalence of delirium when assessed with CAM-ICU and ICDSC. Intensive Care Med 39: 2171-2179.
  32. Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O’Neal PV, Keane KA, et al. (2002) The Richmond agitation-sedation scale: Validity and reliability in adult Intensive Care Unit patients. Am J Respir Crit Care Med 166: 1338-1344.
  33. Hsieh SJ, Soto GJ, Hope AA, Ponea A, Gong MN (2018) The association between acute respiratory distress syndrome, delirium, and in-hospital mortality in Intensive Care Unit patients. Am J Respir Crit Care Med 191: 71-78.
  34. Plaschke K, von Haken R, Scholz M, Engelhardt R, Brobeil A, et al. (2008) Comparison of the confusion assessment method for the Intensive Care Unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) for delirium in critical care patients gives high agreement rate(s). 34: 431-436.
  35. Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, et al. (2001) Delirium in mechanically ventilated patients: Validity and reliability of the confusion assessment method for the Intensive Care Unit (CAM-ICU). JAMA 286: 2703-2710.
  36. Wong CL, Holroyd-Leduc J, Simel DL, Straus SE (2010) Does this patient have delirium? Value of bedside instruments. JAMA 304: 779-786.
  37. Pisani MA, Murphy TE, Araujo KL, Slattum P, Van Ness PH, et al. (2009) Benzodiazepine and opioid use and the duration of Intensive Care Unit delirium in an older population. Crit Care Med 37: 177-183.


Aly MK (2021) Acute Delirium and Difficult Sedation Weaning in ICU Thiamine Deficiency Maybe a Possible not Uncommon Cause. Int J Crit Care Emerg Med 7:131.