Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized controlled trials. (Petrillo)

Wang X, Ding X, Tong Y, Zong J, Zhao X, Ren H, Li Q. Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized controlled trials. J Anesth. 2014 May 24. [Epub ahead of print]

BACKGROUND: Ketamine is traditionally avoided in sedation management of patients with risk of intracranial hypertension. However, results from many clinical trials contradict this concern. We critically analyzed the published data of the effects of ketamine on intracranial pressure (ICP) and other cerebral hemodynamics to determine whether ketamine was safe for patients with hemodynamic instability and brain injuries.

METHODS: We systematically searched the online databases of PubMed, Medline, Embase, Current Controlled Trials, and Cochrane Central (last search performed on January 15, 2014). Trial characteristics and outcomes were independently extracted by two assessors (Xin Wang, Xibing Ding). For continuous data, mean differences (MD) were formulated. If the P value of the chi-square test was >0.10 or I 2 <50 %, a fixed-effects model was used; otherwise, the random effects model was adopted.

RESULTS: Five trials (n = 198) met the inclusion criteria. Using ICP levels within the first 24 h of ketamine administration as the main outcome, the use of ketamine leads to the same ICP levels as opioids [MD = 1.94; 95 % confidence interval (95 % CI), -2.35, 6.23; P = 0.38]. There were no significant differences in mean arterial pressure values between the two groups (MD = 0.99; 95 % CI, -2.24, 4.22; P = 0.55). Ketamine administration was also comparable with opioids in the maintenance of cerebral perfusion pressure (MD = -1.07; 95 % CI, -7.95, 5.8; P = 0.76).

CONCLUSIONS: The results of this study suggest that ketamine does not increase ICP compared with opioids. Ketamine provides good maintenance of hemodynamic status. Clinical application of ketamine should not be discouraged on the basis of ICP-related concerns.

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Age-specific cerebral perfusion pressure thresholds and survival in children and adolescents with severe traumatic brain injury. (Fellow #1 with PCCM)

Allen BB, Chiu YL, Gerber LM, Ghajar J, Greenfield JP. Age-specific cerebral perfusion pressure thresholds and survival in children and adolescents with severe traumatic brain injury*. Pediatr Crit Care Med. 2014 Jan;15(1):62-70.

OBJECTIVES: Evidence-based traumatic brain injury guidelines support cerebral perfusion pressure thresholds for adults at a class 2 level, but evidence is lacking in younger patients. The purpose of this study is to identify the impact of age-specific cerebral perfusion pressure thresholds on short-term survival among patients with severe traumatic brain injury.

DESIGN: Institutional review board-approved, prospective, observational cohort study.

SETTING: Level I or II trauma centers in New York State.

PATIENTS: Data on all patients with a postresuscitation Glasgow Coma Score less than 9 were added in the Brain Trauma Foundation prospective New York State TBI-trac database.

MEASUREMENTS AND MAIN RESULTS: We calculated the survival rates and relative risks of mortality for patients with severe traumatic brain injury based on predefined age-specific cerebral perfusion pressure thresholds. A higher threshold and a lower threshold were defined for each age group: 60 and 50 mm Hg for 12 years old or older, 50 and 35 mm Hg for 6-11 years, and 40 and 30 mm Hg for 0-5 years. Patients were stratified into age groups of 0-11, 12-17, and 18 years old or older. Three exclusive groups of CPP-L (events below low cerebral perfusion pressure threshold), CPP-B (events between high and low cerebral perfusion pressure thresholds), and CPP-H (events above high cerebral perfusion pressure threshold) were defined. As an internal control, we evaluated the associations between cerebral perfusion pressure events and events of hypotension and elevated intracranial pressure. Survival was significantly higher in 0-11 and 18 years old or older age groups for patients with CPP-H events compared with those with CPP-L events. There was a significant decrease in survival with prolonged exposure to CPP-B events for the 0-11 and 18 years old and older age groups when compared with the patients with CPP-H events (p = 0.0001 and p = 0.042, respectively). There was also a significant decrease in survival with prolonged exposure to CPP-L events in all age groups compared with the patients with CPP-H events (p< 0.0001 for 0- to 11-yr olds, p = 0.0240 for 12- to 17-yr olds, and p < 0.0001 for 18-yr old and older age groups). The 12- to 17-year olds had a significantly higher likelihood of survival compared with adults with prolonged exposure to CPP-L events (< 50 mm Hg). CPP-L events were significantly related to systemic hypotension for the 12- to 17-year-old group (p = 0.004) and the 18-year-old and older group (p < 0.0001). CPP-B events were significantly related to systemic hypotension in the 0- to 11-year-old group (p = 0.014). CPP-B and CPP-L events were significantly related to elevated intracranial pressure in all age groups.

CONCLUSIONS: Our data provide new evidence that cerebral perfusion pressure targets should be age specific. Furthermore, cerebral perfusion pressure goals above 50 or 60 mm Hg in adults, above 50 mm Hg in 6- to 17-year olds, and above 40 mm Hg in 0- to 5-year olds seem to be appropriate targets for treatment-based studies. Systemic hypotension had an inconsistent relationship to events of low cerebral perfusion pressure, whereas elevated intracranial pressure was significantly related to all low cerebral perfusion pressure events across all age groups. This may impart a clinically important difference in care, highlighting the necessity of controlling intracranial pressure at all times, while targeting systolic blood pressure in specific instances.

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