Semin Respir Crit Care Med 2019; 40(05): 629-637
DOI: 10.1055/s-0039-1698394
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Circadian Biology and Its Importance to Intensive Care Unit Care and Outcomes

Catherine A. Gao
1   Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
,
Melissa P. Knauert
2   Department of Medicine, Section of Pulmonary and Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut
› Author Affiliations
Further Information

Publication History

Publication Date:
11 December 2019 (online)

Abstract

Circadian rhythms are an integral part of life on earth. Circadian rhythms play a fundamental role in homeostasis as they ensure coordination between the environment and an organism's behavior and physiology. This coordination is called entrainment. Entrainment depends on environmental cues known as zeitgebers. Human zeitgebers include light (primary zeitgeber), sleep, eating, exercise, and activity. Circadian rhythms are disrupted in critically-ill patients due to both critical illness and current intensive care unit (ICU) practices. Disruptions in circadian rhythms are tightly linked with ICU sleep disruption. Together these entities potentiate numerous adverse outcomes including delirium, metabolic derangements, cardiovascular instability, and immune compromise. Herein, we will highlight potential areas for care improvement via chronobundles. We suggest bright light during the day, maintaining darkness, and protecting sleep at night, intermittent rather than continuous feeds, and activity via mobilization during the day. Optimizing circadian rhythms is a low-risk intervention that is underutilized in current ICU practice. This optimization could be a powerful tool in helping to improve outcomes in the critically-ill patient.

 
  • References

  • 1 Takahashi JS. Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet 2017; 18 (03) 164-179
  • 2 Ko CH, Takahashi JS. Molecular components of the mammalian circadian clock. Hum Mol Genet 2006; 15 (Spec No 2): R271-R277
  • 3 Aschoff J. Exogenous and endogenous components in circadian rhythms. Cold Spring Harb Symp Quant Biol 1960; 25: 11-28
  • 4 Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals. Annu Rev Neurosci 2012; 35: 445-462
  • 5 Danielson SJ, Rappaport CA, Loher MK, Gehlbach BK. Looking for light in the din: An examination of the circadian-disrupting properties of a medical intensive care unit. Intensive Crit Care Nurs 2018; 46: 57-63
  • 6 Czeisler CA. The effect of light on the human circadian pacemaker. Ciba Found Symp 1995; 183: 254-290 , discussion 290–302
  • 7 Wright Jr KP, Gooley JJ. Chronobiology mechanisms and circadian sleep disorders. Sleep research society. In: Sleep Research Society; Amlaner CJ, Phill D, Fuller PM. , eds. Basics of Sleep Guide. 2nd ed. Boston, MA: Sleep Research Society; 2009: 11-19
  • 8 Duffy JF, Czeisler CA. Effect of light on human circadian physiology. Sleep Med Clin 2009; 4 (02) 165-177
  • 9 Dewan K, Benloucif S, Reid K, Wolfe LF, Zee PC. Light-induced changes of the circadian clock of humans: increasing duration is more effective than increasing light intensity. Sleep (Basel) 2011; 34 (05) 593-599
  • 10 van Maanen A, Meijer AM, van der Heijden KB, Oort FJ. The effects of light therapy on sleep problems: a systematic review and meta-analysis. Sleep Med Rev 2016; 29: 52-62
  • 11 Ohta H, Yamazaki S, McMahon DG. Constant light desynchronizes mammalian clock neurons. Nat Neurosci 2005; 8 (03) 267-269
  • 12 Danilenko KV, Cajochen C, Wirz-Justice A. Is sleep per se a zeitgeber in humans?. J Biol Rhythms 2003; 18 (02) 170-178
  • 13 Appleman K, Figueiro MG, Rea MS. Controlling light-dark exposure patterns rather than sleep schedules determines circadian phase. Sleep Med 2013; 14 (05) 456-461
  • 14 Mistlberger RE, Skene DJ. Nonphotic entrainment in humans?. J Biol Rhythms 2005; 20 (04) 339-352
  • 15 Mendoza J. Circadian clocks: setting time by food. J Neuroendocrinol 2007; 19 (02) 127-137
  • 16 Asher G, Sassone-Corsi P. Time for food: the intimate interplay between nutrition, metabolism, and the circadian clock. Cell 2015; 161 (01) 84-92
  • 17 Patton DF, Mistlberger RE. Circadian adaptations to meal timing: neuroendocrine mechanisms. Front Neurosci 2013; 7: 185
  • 18 Stokkan KA, Yamazaki S, Tei H, Sakaki Y, Menaker M. Entrainment of the circadian clock in the liver by feeding. Science 2001; 291 (5503): 490-493
  • 19 Rakshit K, Qian J, Colwell CS, Matveyenko AV. The islet circadian clock: entrainment mechanisms, function and role in glucose homeostasis. Diabetes Obes Metab 2015; 17 (Suppl. 01) 115-122
  • 20 Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F, Schibler U. Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 2000; 14 (23) 2950-2961
  • 21 Aschoff J, Fatranská M, Giedke H, Doerr P, Stamm D, Wisser H. Human circadian rhythms in continuous darkness: entrainment by social cues. Science 1971; 171 (3967): 213-215
  • 22 Mistlberger RE, Skene DJ. Social influences on mammalian circadian rhythms: animal and human studies. Biol Rev Camb Philos Soc 2004; 79 (03) 533-556
  • 23 Hower IM, Harper SA, Buford TW. Circadian rhythms, exercise, and cardiovascular health. J Circadian Rhythms 2018; 16: 7
  • 24 Harfmann BD, Schroder EA, Esser KA. Circadian rhythms, the molecular clock, and skeletal muscle. J Biol Rhythms 2015; 30 (02) 84-94
  • 25 Yamanaka Y, Hashimoto S, Tanahashi Y, Nishide S-Y, Honma S, Honma K. Physical exercise accelerates reentrainment of human sleep-wake cycle but not of plasma melatonin rhythm to 8-h phase-advanced sleep schedule. Am J Physiol Regul Integr Comp Physiol 2010; 298 (03) R681-R691
  • 26 Rensing L, Ruoff P. Temperature effect on entrainment, phase shifting, and amplitude of circadian clocks and its molecular bases. Chronobiol Int 2002; 19 (05) 807-864
  • 27 Refinetti R. Entrainment of circadian rhythm by ambient temperature cycles in mice. J Biol Rhythms 2010; 25 (04) 247-256
  • 28 Claustrat B, Brun J, Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev 2005; 9 (01) 11-24
  • 29 Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS, Slominski AT. Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol 2012; 351 (02) 152-166
  • 30 Morgenthaler T, Alessi C, Friedman L. , et al; Standards of Practice Committee; American Academy of Sleep Medicine. Practice parameters for the use of actigraphy in the assessment of sleep and sleep disorders: an update for 2007. Sleep 2007; 30 (04) 519-529
  • 31 Fan EP, Abbott SM, Reid KJ, Zee PC, Maas MB. Abnormal environmental light exposure in the intensive care environment. J Crit Care 2017; 40: 11-14
  • 32 Craig T, Mathieu S. CANDLE: The critical analysis of the nocturnal distribution of light exposure - A prospective pilot study quantifying the nocturnal light intensity on a critical care unit. J Intensive Care Soc 2018; 19 (03) 196-200
  • 33 Knauert MP, Pisani M, Redeker N. , et al. Pilot study: an intensive care unit sleep promotion protocol. BMJ Open Respir Res 2019; 6 (01) e000411
  • 34 Durrington HJ, Clark R, Greer R. , et al. ‘In a dark place, we find ourselves’: light intensity in critical care units. Intensive Care Med Exp 2017; 5 (01) 9
  • 35 Pisani MA, Friese RS, Gehlbach BK, Schwab RJ, Weinhouse GL, Jones SF. Sleep in the intensive care unit. Am J Respir Crit Care Med 2015; 191 (07) 731-738
  • 36 Knauert MP, Yaggi HK, Redeker NS, Murphy TE, Araujo KL, Pisani MA. Feasibility study of unattended polysomnography in medical intensive care unit patients. Heart Lung 2014; 43 (05) 445-452
  • 37 Giusti GD, Tuteri D, Giontella M. Nursing interactions with intensive care unit patients affected by sleep deprivation: an observational study. Dimens Crit Care Nurs 2016; 35 (03) 154-159
  • 38 Berglund B, Lindvall T, Schwela DH. New WHO guidelines for community noise. noise & vibration worldwide 2000; 31: 24-29
  • 39 Tainter CR, Levine AR, Quraishi SA. , et al. Noise levels in surgical ICUs are consistently above recommended standards. Crit Care Med 2016; 44 (01) 147-152
  • 40 Busch-Vishniac IJ, West JE, Barnhill C, Hunter T, Orellana D, Chivukula R. Noise levels in Johns Hopkins Hospital. J Acoust Soc Am 2005; 118 (06) 3629-3645
  • 41 Darbyshire JL, Young JD. An investigation of sound levels on intensive care units with reference to the WHO guidelines. Crit Care 2013; 17 (05) R187
  • 42 Freedman NS, Gazendam J, Levan L, Pack AI, Schwab RJ. Abnormal sleep/wake cycles and the effect of environmental noise on sleep disruption in the intensive care unit. Am J Respir Crit Care Med 2001; 163 (02) 451-457
  • 43 Knauert M, Jeon S, Murphy TE, Yaggi HK, Pisani MA, Redeker NS. Comparing average levels and peak occurrence of overnight sound in the medical intensive care unit on A-weighted and C-weighted decibel scales. J Crit Care 2016; 36: 1-7
  • 44 Tamburri LM, DiBrienza R, Zozula R, Redeker NS. Nocturnal care interactions with patients in critical care units. Am J Crit Care 2004; 13 (02) 102-112 , quiz 114–115
  • 45 Le A, Friese RS, Hsu C-H, Wynne JL, Rhee P, O'Keeffe T. Sleep disruptions and nocturnal nursing interactions in the intensive care unit. J Surg Res 2012; 177 (02) 310-314
  • 46 McClave SA, Martindale RG, Vanek VW. , et al; A.S.P.E.N. Board of Directors; American College of Critical Care Medicine; Society of Critical Care Medicine. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2009; 33 (03) 277-316
  • 47 Yasumoto Y, Hashimoto C, Nakao R. , et al. Short-term feeding at the wrong time is sufficient to desynchronize peripheral clocks and induce obesity with hyperphagia, physical inactivity and metabolic disorders in mice. Metabolism 2016; 65 (05) 714-727
  • 48 Cissé YM, Borniger JC, Lemanski E, Walker II WH, Nelson RJ. Time-restricted feeding alters the innate immune response to bacterial endotoxin. J Immunol 2018; 200 (02) 681-687
  • 49 Oyama Y, Iwasaka H, Koga H, Shingu C, Matsumoto S, Noguchi T. Uncoupling of peripheral and master clock gene rhythms by reversed feeding leads to an exacerbated inflammatory response after polymicrobial sepsis in mice. Shock 2014; 41 (03) 214-221
  • 50 Marik PE. Feeding critically ill patients the right ‘whey’: thinking outside of the box. A personal view. Ann Intensive Care 2015; 5 (01) 51
  • 51 Hodgson C, Bellomo R, Berney S. , et al; TEAM Study Investigators. Early mobilization and recovery in mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study. Crit Care 2015; 19: 81
  • 52 Frisk U, Olsson J, Nylén P, Hahn RG. Low melatonin excretion during mechanical ventilation in the intensive care unit. Clin Sci (Lond) 2004; 107 (01) 47-53
  • 53 Gehlbach BK, Chapotot F, Leproult R. , et al. Temporal disorganization of circadian rhythmicity and sleep-wake regulation in mechanically ventilated patients receiving continuous intravenous sedation. Sleep (Basel) 2012; 35 (08) 1105-1114
  • 54 Ben-Hamouda N, Poirel V-J, Dispersyn G, Pévet P, Challet E, Pain L. Short-term propofol anaesthesia down-regulates clock genes expression in the master clock. Chronobiol Int 2018; 35 (12) 1735-1741
  • 55 Dimsdale JE, Norman D, DeJardin D, Wallace MS. The effect of opioids on sleep architecture. J Clin Sleep Med 2007; 3 (01) 33-36
  • 56 Poulsen RC, Warman GR, Sleigh J, Ludin NM, Cheeseman JF. How does general anaesthesia affect the circadian clock?. Sleep Med Rev 2018; 37: 35-44
  • 57 Haimovich B, Calvano J, Haimovich AD, Calvano SE, Coyle SM, Lowry SF. In vivo endotoxin synchronizes and suppresses clock gene expression in human peripheral blood leukocytes. Crit Care Med 2010; 38 (03) 751-758
  • 58 Mundigler G, Delle-Karth G, Koreny M. , et al. Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis. Crit Care Med 2002; 30 (03) 536-540
  • 59 Li C-X, Liang D-D, Xie G-H. , et al. Altered melatonin secretion and circadian gene expression with increased proinflammatory cytokine expression in early-stage sepsis patients. Mol Med Rep 2013; 7 (04) 1117-1122
  • 60 Gazendam JAC, Van Dongen HPA, Grant DA, Freedman NS, Zwaveling JH, Schwab RJ. Altered circadian rhythmicity in patients in the ICU. Chest 2013; 144 (02) 483-489
  • 61 Duclos C, Dumont M, Wiseman-Hakes C. , et al. Sleep and wake disturbances following traumatic brain injury. Pathol Biol (Paris) 2014; 62 (05) 252-261
  • 62 Paul T, Lemmer B. Disturbance of circadian rhythms in analgosedated intensive care unit patients with and without craniocerebral injury. Chronobiol Int 2007; 24 (01) 45-61
  • 63 Zager A, Andersen ML, Ruiz FS, Antunes IB, Tufik S. Effects of acute and chronic sleep loss on immune modulation of rats. Am J Physiol Regul Integr Comp Physiol 2007; 293 (01) R504-R509
  • 64 Carlson DE, Chiu WC. The absence of circadian cues during recovery from sepsis modifies pituitary-adrenocortical function and impairs survival. Shock 2008; 29 (01) 127-132
  • 65 Fonken LK, Bedrosian TA, Zhang N, Weil ZM, DeVries AC, Nelson RJ. Dim light at night impairs recovery from global cerebral ischemia. Exp Neurol 2019; 317: 100-109
  • 66 Weinhouse GL, Schwab RJ, Watson PL. , et al. Bench-to-bedside review: delirium in ICU patients - importance of sleep deprivation. Crit Care 2009; 13 (06) 234
  • 67 Devlin JW, Skrobik Y, Gélinas C. , et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018; 46 (09) e825-e873
  • 68 Pisani MA, Kong SYJ, Kasl SV, Murphy TE, Araujo KLB, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009; 180 (11) 1092-1097
  • 69 Kamdar BB, King LM, Collop NA. , et al. The effect of a quality improvement intervention on perceived sleep quality and cognition in a medical ICU. Crit Care Med 2013; 41 (03) 800-809
  • 70 Patel SR, Malhotra A, Gao X, Hu FB, Neuman MI, Fawzi WW. A prospective study of sleep duration and pneumonia risk in women. Sleep (Basel) 2012; 35 (01) 97-101
  • 71 Faraut B, Boudjeltia KZ, Vanhamme L, Kerkhofs M. Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery. Sleep Med Rev 2012; 16 (02) 137-149
  • 72 Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet 1999; 354 (9188): 1435-1439
  • 73 Frey DJ, Fleshner M, Wright Jr KP. The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun 2007; 21 (08) 1050-1057
  • 74 Prather AA, Janicki-Deverts D, Hall MH, Cohen S. Behaviorally assessed sleep and susceptibility to the common cold. Sleep (Basel) 2015; 38 (09) 1353-1359
  • 75 Jeyaraj D, Haldar SM, Wan X. , et al. Circadian rhythms govern cardiac repolarization and arrhythmogenesis. Nature 2012; 483 (7387): 96-99
  • 76 Hu R-F, Jiang X-Y, Chen J. , et al. Non-pharmacological interventions for sleep promotion in the intensive care unit. Cochrane Database Syst Rev 2015; (10) CD008808
  • 77 Oldham MA, Lee HB, Desan PH. Circadian rhythm disruption in the critically ill: an opportunity for improving outcomes. Crit Care Med 2016; 44 (01) 207-217
  • 78 Gehlbach BK, Patel SB, Van Cauter E, Pohlman AS, Hall JB, Zabner J. The effects of timed light exposure in critically ill patients: a randomized controlled pilot clinical trial. Am J Respir Crit Care Med 2018; 198 (02) 275-278
  • 79 Taguchi T, Yano M, Kido Y. Influence of bright light therapy on postoperative patients: a pilot study. Intensive Crit Care Nurs 2007; 23 (05) 289-297
  • 80 Simons KS, Laheij RJ, van den Boogaard M. , et al. Dynamic light application therapy to reduce the incidence and duration of delirium in intensive-care patients: a randomised controlled trial. Lancet Respir Med 2016; 4 (03) 194-202
  • 81 Pustjens T, Schoutens AM, Janssen L, Heesen WF. Effect of dynamic light at the coronary care unit on the length of hospital stay and development of delirium: a retrospective cohort study. J Geriatr Cardiol 2018; 15 (09) 567-573
  • 82 Hu R-F, Jiang X-Y, Zeng Y-M, Chen X-Y, Zhang Y-H. Effects of earplugs and eye masks on nocturnal sleep, melatonin and cortisol in a simulated intensive care unit environment. Crit Care 2010; 14 (02) R66
  • 83 Demoule A, Carreira S, Lavault S. , et al. Impact of earplugs and eye mask on sleep in critically ill patients: a prospective randomized study. Crit Care 2017; 21 (01) 284
  • 84 Knauert MP, Redeker NS, Yaggi HK, Bennick M, Pisani MA. Creating naptime: an overnight, nonpharmacologic intensive care unit sleep promotion protocol. J Patient Exp 2018; 5 (03) 180-187
  • 85 McClave SA, Taylor BE, Martindale RG. , et al; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016; 40 (02) 159-211
  • 86 Nasiri M, Farsi Z, Ahangari M, Dadgari F. Comparison of intermittent and bolus enteral feeding methods on enteral feeding intolerance of patients with sepsis: a triple-blind controlled trial in intensive care units. Middle East J Dig Dis 2017; 9 (04) 218-227
  • 87 Sunderram J, Sofou S, Kamisoglu K, Karantza V, Androulakis IP. Time-restricted feeding and the realignment of biological rhythms: translational opportunities and challenges. J Transl Med 2014; 12: 79
  • 88 Hodgson CL, Capell E, Tipping CJ. Early mobilization of patients in intensive care: organization, communication and safety factors that influence translation into clinical practice. Crit Care 2018; 22 (01) 77
  • 89 Nydahl P, Sricharoenchai T, Chandra S. , et al. Safety of patient mobilization and rehabilitation in the intensive care unit. systematic review with meta-analysis. Ann Am Thorac Soc 2017; 14 (05) 766-777
  • 90 Tipping CJ, Harrold M, Holland A, Romero L, Nisbet T, Hodgson CL. The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review. Intensive Care Med 2017; 43 (02) 171-183
  • 91 Kayambu G, Boots R, Paratz J. Physical therapy for the critically ill in the ICU: a systematic review and meta-analysis. Crit Care Med 2013; 41 (06) 1543-1554
  • 92 Lewis SR, Pritchard MW, Schofield-Robinson OJ, Alderson P, Smith AF. Melatonin for the promotion of sleep in adults in the intensive care unit. Cochrane Database Syst Rev 2018; 5: CD012455
  • 93 Huang H-W, Zheng B-L, Jiang L. , et al. Effect of oral melatonin and wearing earplugs and eye masks on nocturnal sleep in healthy subjects in a simulated intensive care unit environment: which might be a more promising strategy for ICU sleep deprivation?. Crit Care 2015; 19: 124
  • 94 Shilo L, Dagan Y, Smorjik Y. , et al. Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study. Chronobiol Int 2000; 17 (01) 71-76
  • 95 Mo Y, Scheer CE, Abdallah GT. Emerging role of melatonin and melatonin receptor agonists in sleep and delirium in intensive care unit patients. J Intensive Care Med 2016; 31 (07) 451-455
  • 96 Baumgartner L, Lam K, Lai J. , et al. Effectiveness of melatonin for the prevention of intensive care unit delirium. Pharmacotherapy 2019; 39 (03) 280-287
  • 97 Marra A, McGrane TJ, Henson CP, Pandharipande PP. Melatonin in critical care. Crit Care Clin 2019; 35 (02) 329-340
  • 98 Alexopoulou C, Kondili E, Diamantaki E. , et al. Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study. Anesthesiology 2014; 121 (04) 801-807
  • 99 Skrobik Y, Duprey MS, Hill NS, Devlin JW. Low-dose nocturnal dexmedetomidine prevents icu delirium. a randomized, placebo-controlled trial. Am J Respir Crit Care Med 2018; 197 (09) 1147-1156