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Hypothermia, immune suppression and SDD: can we have our cake and eat it?

Abstract

In vitro studies and clinical observations suggest that both accidental and controlled/therapeutic hypothermia have a strong immunosuppressive effect, and that hypothermia increases the risk of infections, especially wound infections and pneumonia. In the previous issue of Critical Care, Kamps and colleagues report that when hypothermia was used for prolonged periods in patients with severe traumatic brain injury in conjunction with selective decontamination of the digestive tract, the risks of infection were the same or lower in patients treated with therapeutic cooling. The risk of infection is widely regarded as the most important danger of therapeutic cooling. The findings of Kamps and colleagues need to be verified in prospective trials and in higher-resistance environments, but raise the possibility of cooling for prolonged periods with greatly reduced risk. We may be able to have our cake and eat it.

In the previous issue of Critical Care, Kamps and colleagues reported a surprising observation, one that at first glance contradicts perceived knowledge on therapeutic cooling [1]. Numerous studies have shown that hypothermia can prevent or mitigate ischaemia/reperfusion injuries, and can be used to treat brain oedema [2–4]. There is a growing list of potential indications, although many applications still await evaluation in rigorous clinical trials [4]. In recent years the mechanisms through which hypothermia provides tissue protection have been studied extensively [3]. One key mechanism is the inhibition of a harmful proinflammatory cascade that develops in injured organs following traumatic or ischaemic injuries [3]. Many animal experiments and clinical studies have shown that hypothermia can suppress these harmful inflammatory reactions, and block the release of proinflammatory cytokines [5–8]. Hypothermia can also decrease production of leukotrienes and nitric oxide, prevent reperfusion-related DNA injury and lipid peroxidation, and impair neutrophil and macrophage function. At temperatures <32 to 33°C, hypothermia can decrease the white blood cell count [2, 3].

The proinflammatory response, however, is not purely harmful. Some reactions are helpful in tissue repair, and the good may be inhibited along with the bad [9–12]. Moreover, suppression of inflammatory responses occurs in all organs, not just the injured ones, and inhibition of immune response can lead to an increased risk of infections. In this sense, hypothermia is a two-edged sword: the mechanism that provides tissue protection can simultaneously hamper the bodies' ability to fight infections. This problem can be compounded by hypothermia-associated hyperglycaemia, which can further increase the infection risks [3].

Many clinical studies have indeed found higher infection rates in patients treated with prolonged (> 24 hours) therapeutic cooling [4]. For example, in a recently published study in patients with ischaemic stroke, the rate of pneumonia was 50% in patients treated with hypothermia versus 10% in controls. Nevertheless, out-comes were better in the hypothermia group, in spite of these adverse events [13]. Most studies on therapeutic cooling have reported trends or significantly higher infection rates in patients treated with cooling, with the risks appearing to increase with longer treatment periods [4]. The increase in infection risk may be even greater with accidental hypothermia [14].

Based on the physiological data and the clinical studies discussed above, some increase in infection risk is usually regarded as an unavoidable consequence of hypothermia treatment. Duration of cooling therapy is often limited because of the (perceived) risk of infections. Few of the clinical trials performed so far, however, have used standard decontamination of the digestive tract (SDD) or other forms of antibiotic prophylaxis in their patients.

In the previous issue of Critical Care, Kamps and coworkers report on their use of prolonged therapeutic cooling to control intracranial pressure in patients with severe traumatic brain injury, in a setting where SDD was routinely used [1]. They compared infection rates in 35 patients treated with hypothermia (median duration 107 hours) with 169 controls matched for severity of injury, age, and other relevant factors. SDD was used in all patients. The overall risk of any infection was 20% for hypothermia patients, versus 34.4% in controls. Most notably, the risk of ventilator-associated pneumonia was the same in patients treated with hypothermia compared with matched controls.

These findings may come as a surprise, but they are in line with two previous studies using prolonged hypothermia in combination with SDD [15, 16]. These studies also reported low infection rates in patients treated with hypothermia and SDD, and found that infection rates were the same or lower than in controls.

Many studies have shown that SDD can reduce Gram-negative infection rates, and some have reported reductions in intensive care unit mortality [17]. The findings of Kamps and colleagues suggest that SDD could help avoid one of the most important complications of therapeutic cooling. Their findings need to be confirmed in larger, prospective studies, and the efficacy of SDD in environments with a higher incidence of resistant micro-organisms needs to be determined. The study by Kamps and colleagues provides an exciting starting point, and opens up possibilities for exploring long-term hypothermia treatments.

Abbreviations

SDD:

standard decontamination of the digestive tract.

References

  1. Kamps M, Bisschops L, van der Hoeven JG, Hoedemaekers CWE: Hypothermia does not increase the risk of infection: a case control study. Crit Care 2011, 15: R48. 10.1186/cc10012

    Article  PubMed Central  PubMed  Google Scholar 

  2. Polderman KH: Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med 2009, 37: S186-S202. 10.1097/CCM.0b013e3181aa5241

    Article  PubMed  Google Scholar 

  3. Polderman KH, Herold I: Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med 2009, 37: 1101-1120. 10.1097/CCM.0b013e3181962ad5

    Article  PubMed  Google Scholar 

  4. Polderman KH: Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet 2008, 371: 1955-1969. 10.1016/S0140-6736(08)60837-5

    Article  PubMed  Google Scholar 

  5. Aibiki M, Maekawa S, Ogura S, Kinoshita Y, Kawai N, Yokono S: Effect of moderate hypothermia on systemic and internal jugular plasma IL-6 levels after traumatic brain injury in humans. J Neurotrauma 1999, 16: 225-232. 10.1089/neu.1999.16.225

    Article  CAS  PubMed  Google Scholar 

  6. Kimura A, Sakurada S, Ohkuni H, Todome Y, Kurata K: Moderate hypothermia delays proinflammatory cytokine production of human peripheral blood mononuclear cells. Crit Care Med 2002, 30: 1499-1502. 10.1097/00003246-200207000-00017

    Article  CAS  PubMed  Google Scholar 

  7. Suehiro E, Fujisawa H, Akimura T, Ishihara H, Kajiwara K, Kato S, Fujii M, Yamashita S, Maekawa T, Suzuki M: Increased matrix metalloproteinase-9 in blood in association with activation of interleukin-6 after traumatic brain injury: influence of hypothermic therapy. J Neurotrauma 2004, 21: 1706-1711. 10.1089/neu.2004.21.1706

    Article  PubMed  Google Scholar 

  8. Dietrich WD, Chatzipanteli K, Vitarbo E, Wada K, Kinoshita K: The role of inflammatory processes in the pathophysiology and treatment of brain and spinal cord trauma. Acta Neurochir Suppl 2004, 89: 69-74.

    CAS  PubMed  Google Scholar 

  9. Schmidt OI, Heyde CE, Ertel W, Stahel PF: Closed head injury - an inflammatory disease? Brain Res Brain Res Rev 2005, 48: 388-399. 10.1016/j.brainresrev.2004.12.028

    Article  PubMed  Google Scholar 

  10. Asensio VC, Campbell IL: Chemokines in the CNS: plurifunctional mediators in diverse states. Trends Neurosci 1999, 22: 504-512. 10.1016/S0166-2236(99)01453-8

    Article  CAS  PubMed  Google Scholar 

  11. Merrill JE, Benveniste EN: Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci 1996, 19: 331-338. 10.1016/0166-2236(96)10047-3

    Article  CAS  PubMed  Google Scholar 

  12. Morganti-Kossmann MC, Rancan M, Stahel PF, Kossmann T: Inflamatory response in acute traumatic brain injury: a double-edged sword. Curr Opin Crit Care 2002, 8: 101-105. 10.1097/00075198-200204000-00002

    Article  PubMed  Google Scholar 

  13. Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, Wijman CA, Rapp KS, Grotta JC, Lyden PD, ICTuS-L Investigators: Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke 2010, 41: 2265-2270. 10.1161/STROKEAHA.110.592295

    Article  PubMed Central  PubMed  Google Scholar 

  14. Kurz A, Sessler DI, Lenhardt R, Study of Wound Infection and Temperature Group: Perioperative normothermia to reduce the incidence of surgicalwound infection and shorten hospitalization. N Engl J Med 1996, 334: 1209-1215. 10.1056/NEJM199605093341901

    Article  CAS  PubMed  Google Scholar 

  15. Polderman KH, Tjong Tjin Joe R, Peerdeman SM, Vandertop WP, Girbes AR: Effects of therapeutic hypothermia on intracranial pressure and outcome in patients with severe head injury. Intensive Care Med 2002, 28: 1563-1573. 10.1007/s00134-002-1511-3

    Article  PubMed  Google Scholar 

  16. Polderman KH, Peerdeman SM, Girbes AR: Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury. J Neurosurg 2001, 94: 697-705. 10.3171/jns.2001.94.5.0697

    Article  CAS  PubMed  Google Scholar 

  17. de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, Bernards AT, Kuijper EJ, Joore JC, Leverstein-van Hall MA, Bindels AJ, Jansz AR, Wesselink RM, de Jongh BM, Dennesen PJ, van Asselt GJ, te Velde LF, Frenay IH, Kaasjager K, Bosch FH, van Iterson M, Thijsen SF, Kluge GH, Pauw W, de Vries JW, Kaan JA, et al.: Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med 2009, 360: 20-31. 10.1056/NEJMoa0800394

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Kees H Polderman.

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Polderman, K.H. Hypothermia, immune suppression and SDD: can we have our cake and eat it?. Crit Care 15, 144 (2011). https://doi.org/10.1186/cc10080

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