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THE RATIONAL CLINICIAN’S CORNER

CLINICAL EXAMINATION

How Do I Perform a Lumbar Puncture


and Analyze the Results to Diagnose
Bacterial Meningitis?
Sharon E. Straus, MD, MSc, FRCPC Context Diagnostic lumbar punctures (LPs), commonly used to rule out meningitis,
Kevin E. Thorpe, MMath are associated with adverse events.
Jayna Holroyd-Leduc, MD, FRCPC Objective To systematically review the evidence about diagnostic LP techniques that
may decrease the risk of adverse events and the evidence about test accuracy of cere-
PATIENT SCENARIO brospinal fluid (CSF) analysis in adult patients with suspected bacterial meningitis.
A previously healthy 70-year-old Data Sources We searched the Cochrane Library, MEDLINE (using Ovid and PubMed)
woman presents to the emergency de- from 1966 to January 2006 and EMBASE from 1980 to January 2006 without lan-
partment with a 3-day history of fe- guage restrictions to identify relevant studies and identified others from the bibliog-
raphies of retrieved articles.
ver, confusion, and lethargy. She is un-
able to cooperate with a full physical Study Selection We included randomized trials of patients aged 18 years or older
examination, but she has neck stiff- undergoing interventions to facilitate a successful diagnostic LP or to potentially re-
duce adverse events. Studies assessing the accuracy of biochemical analysis of the CSF
ness upon neck flexion. Her score on
for possible bacterial meningitis were also identified.
the Glasgow Coma Scale is 13 (eye, 4;
verbal, 4; motor, 5). The findings from Data Extraction Two investigators independently appraised study quality and ex-
a chest radiograph and urinalysis are tracted relevant data. For studies of the LP technique, data on the intervention and
the outcome were extracted. For studies of the laboratory diagnosis of bacterial men-
normal.1 You seek consent from her ingitis, data on the reference standard and test accuracy were extracted.
husband to perform a lumbar punc-
ture (LP). Data Synthesis We found 15 randomized trials. A random-effects model was used
for quantitative synthesis. Five studies of 587 patients compared atraumatic needles with
Why Is This Diagnostic Procedure standard needles and found a nonsignificant decrease in the odds of headache with an
atraumatic needle (absolute risk reduction [ARR], 12.3%; 95% confidence interval [CI],
Important?
−1.72% to 26.2%). Reinsertion of the stylet before needle removal decreased the risk of
In a previous Rational Clinical Exami- headache (ARR, 11.3%; 95% CI, 6.50%-16.2%). The combined results from 4 studies
nation article, Attia and colleagues1 dis- of 717 patients showed a nonsignificant decrease in headache in patients who were mo-
cussed the above scenario and recom- bilized after LP (ARR, 2.9%; 95% CI, −3.4 to 9.3%). Four studies on the accuracy of
mended proceeding to LP for definitive biochemical analysis of CSF in patients with suspected meningitis met inclusion criteria. A
testing of the cerebrospinal fluid (CSF). CSF–blood glucose ratio of 0.4 or less (likelihood ratio [LR], 18; 95% CI, 12-27]), CSF
white blood cell count of 500/µL or higher (LR, 15; 95% CI, 10-22), and CSF lactate
Cerebrospinal fluid is a clear, color-
level of 31.53 mg/dL or more (ⱖ3.5 mmol/L; LR, 21; 95% CI, 14-32) accurately diag-
less fluid that fills the ventricles and nosed bacterial meningitis.
subarachnoid space surrounding the
brain and spinal cord.2 Lumbar punc- Conclusions These data suggest that small-gauge, atraumatic needles may de-
crease the risk of headache after diagnostic LP. Reinsertion of the stylet before needle
ture allows this fluid to be sampled, removal should occur and patients do not require bed rest after the procedure. Future
facilitating the diagnosis of various research should focus on evaluating interventions to optimize the success of a diag-
conditions. nostic LP and to enhance training in procedural skills.
Since it was first described by JAMA. 2006;296:2012-2022 www.jama.com
Quincke3 in 1891, the LP has become
Author Affiliations: Division of General Internal Medi- Corresponding Author: Sharon E. Straus, MD, MSc,
cine,UniversityofCalgary,Alberta(DrStraus);Knowledge FRCPC, Foothills Medical Centre 1403 29th St NW, Cal-
Translation Program, University of Toronto/St Mi- gary, Canada AB T2N 2T9 (sharon.straus@utoronto.ca).
See also Patient Page. chael’sHospital,Toronto,Ontario(DrsStrausandHolroyd- The Rational Clinical Examination Section Editors:
Leduc and Mr Thorpe); Department of Public Health David L. Simel, MD, MHS, Durham Veterans Affairs
CME available online at Sciences, University of Toronto, Toronto, Ontario (Mr Medical Center and Duke University Medical Center,
www.jama.com Thorpe); Division of General Internal Medicine, Univer- Durham, NC; Drummond Rennie, MD, Deputy Edi-
sityHealthNetwork,Toronto,Ontario(DrHolroyd-Leduc). tor, JAMA.

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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE

an important diagnostic tool, particu- 95% confidence interval [CI], 1.5-3.2), therapy. There was a trend toward in-
larly when considering the diagnosis of focal neurological finding (LR, 4.3; 95% creased risk of paraparesis in the anti-
meningitis. Evaluation of CSF can help CI, 1.9-10), and papilledema (LR, 11; coagulated patients (relative risk, 11.0;
establish a diagnosis and guide antimi- 95% CI, 1.1-115) increased the likeli- 95% CI, 0.60-199) with 5 patients in
crobial therapy. Less commonly, LP is hood of an intracranial lesion.12 Over- the anticoagulation group experienc-
used as part of the diagnostic workup all clinical impression (not defined in the ing an adverse event compared with
of patients with suspected subarach- study) was able to identify patients with none in the control group. In all pa-
noid hemorrhage, demyelinating dis- a CT-defined contraindication to LP (LR, tients who experienced paraparesis, an-
ease, and leptomeningeal metastasis.4,5 19; 95% CI, 4.8-43). In a second pro- ticoagulation had been started within
spective study of 301 patients with sus- an hour of the procedure.14 A survey of
What Adverse Events Can Result pected meningitis, 235 underwent a CT 246 pediatric and adult neurology de-
From an LP? scan prior to LP.13 The mean age of pa- partment chairpersons and residency
Bier was the first to report the tech- tients was 40 years (16% were ⱖ60 program directors found that 45% of re-
nique of spinal anesthesia and also pro- years), 25% were immunocompro- spondents ordered platelet and antico-
vided (through personal experience!) mised, and 27% of patients had a Charl- agulation studies prior to LP.15 We were
the first description of post-LP head- son comorbidity score of more than 1. unable to find any data evaluating the
ache.6 Headache and backache are the Patients were assessed clinically by an safety of LP in patients with low plate-
most frequently reported adverse events emergency physician or general inter- let counts. In a case series of 66 pa-
associated with LP. Headache can oc- nist. The absence of a number of clini- tients with acute leukemia, patients
cur in up to 60% of patients who un- cal features at baseline was able to iden- with lower platelet counts (⬍50⫻103/
dergo the procedure, although esti- tify those who were unlikely to have an µL) had higher risk of a traumatic pro-
mates vary due to differences in abnormal CT result (LR, 0.10; 95% CI, cedure as defined by the presence in the
inclusion criteria and definitions of 0.03-0.31). The absence of all of the fol- CSF of more than 500 red blood cells
headache.7-9 Headache can be severe and lowing baseline characteristics was as- per high-powered field.16 However, LPs
debilitating10 and is believed to occur sociated with this low LR: age 60 years were not performed in patients with
because of CSF leakage through the du- or older, immunocompromised state, platelet counts lower than 20 ⫻103/µL
ral puncture site.11 Backache is less com- history of central nervous system dis- in this study.
mon but can occur in up to 40% of pa- ease, and seizure within 1 week of pre- We conducted a systematic review to
tients following LP.7 Rare adverse events sentation. In addition, there could be identify studies of interventions that en-
include cerebral herniation, intracra- none of the following physical exami- hance the success of an LP and that mini-
nial subdural hemorrhage, spinal epi- nation findings: abnormal level of con- mize adverse events. Based on review of
dural hemorrhage, and infection.11 sciousness, inability to answer 2 ques- the evidence and its integration with ex-
tions correctly, inability to follow 2 pert opinion, we provide a best-
What Are the Contraindications consecutive commands correctly, gaze practice approach for LP in adults. Be-
to Performing an LP? palsy, abnormal visual fields, facial palsy, cause a clinician’s interpretation of the
Clinicians often worry that an undetec- arm drift, leg drift, and abnormal lan- LP results is tightly coupled to the clini-
ted mass lesion or ventricular obstruc- guage. Using the pretest probability of cal examination findings, we also re-
tion causing raised intracranial pres- an abnormal CT finding from this study viewed the literature that addresses the
sure pose risks for cerebral herniation (23.8%), the absence of all of these fea- accuracy of common CSF tests for bac-
following an LP.4 However, no conclu- tures would reduce the probability of an terial meningitis. Tests for diagnosing vi-
sive evidence supports that the risk can abnormal finding to 3.0%. The find- ral meningitis were not included in this
be reduced with universal neuroimag- ings from these 2 studies have not been review. Although there are other indi-
ing prior to LP. Instead of universal neu- validated prospectively in other inde- cations for LP and CSF analysis, this ar-
roimaging, clinicians can use the clini- pendent populations. ticle focuses on CSF analysis for sus-
cal examination to guide the decision to Local infection at the puncture site pected bacterial meningitis because it
obtain neuroimaging. In a prospective is also a contraindication to complet- requires immediate action and is one of
study, 113 patients were examined by ing an LP but this occurs infre- the most common diagnoses that gen-
internal medicine residents (overseen by quently.4 More frequently, clinicians are eralist physicians consider when per-
emergency physicians) prior to under- concerned about coagulation defects forming this procedure.
going computed tomography (CT) of the and use of anticoagulants, which may
brain and subsequent LP.12 The me- increase the risk of epidural hemor- METHODS
dian age of patients was 42 years, 36% rhage. In 1 study of post-LP complica- Searches of the Cochrane Library,
were immunocompromised, and 46% of tions, outcomes were compared in 166 MEDLINE (using Ovid and PubMed)
patients had altered mentation. Altered patients receiving anticoagulation with from 1966 to January 2006, and
mentation (likelihood ratio [LR], 2.2; 171 of those who were not receiving EMBASE from 1980 to January 2006
©2006 American Medical Association. All rights reserved. (Reprinted) JAMA, October 25, 2006—Vol 296, No. 16 2013

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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE

were completed to identify relevant Two reviewers (S.E.S. and J.M. .r-project.org). A 2-tailed P value of
studies. The search strategy used the H-L.) independently reviewed and se- ⬍.05 was considered statistically sig-
terms lumbar puncture, spinal punc- lected relevant publications that met the nificant.
ture, dural puncture, headache, head- inclusion criteria from the search re-
ach*, spinal needle*, cerebrospinal fluid, sults. Disagreements were resolved by RESULTS
spinal fluid, and meningitis. Interven- consensus. In cases of doubt, full-text We found 537 citations of potential in-
tion studies were limited to random- articles were retrieved for review and terventions to optimize LP technique.
ized controlled trials using the terms discussion. Full-text articles of all ab- Review of these led to retrieval of 22
randomized controlled trial, controlled stracts that met the inclusion criteria full-text articles for assessment, 15 of
clinical trial, clinical trial, random allo- were retrieved. which were subsequently identified for
cation, and random*. No language re- The 2 reviewers independently read inclusion. Reasons for excluding trials
strictions were used. Additional ar- all full-text articles to confirm that in- were lack of randomization (5 stud-
ticles were identified from searching the clusion criteria were met. The investi- ies18-22), repeat publication (1 study23),
bibliographies of retrieved articles. De- gators also assessed study quality. For and inability to obtain outcomes data
tails on the search strategies are avail- intervention studies, a specially de- (1 study24). Studies were categorized by
able on request. signed data collection form was used to intervention including needle type,
Randomized trials of patients (ⱖ18 extract data on study quality includ- needle size, reinsertion of stylet, mo-
years) undergoing interventions to po- ing the method of randomization, the bilization after LP, and use of supple-
tentially reduce headache and back- presence of blinding, and the method mental fluids. No studies of other in-
ache at the time of diagnostic LP were used for outcome assessment. Data were terventions—such as positioning of the
included. However, if no randomized also extracted on the intervention and patient during LP, direction of bevel,
studies of a particular intervention were the dichotomous outcome variable of volume of CSF removed, or prophy-
identified, studies of lower quality— post-LP headache. The minimum in- lactic use of an epidural blood patch—
including cohort, case-control, and case clusion criteria for randomized stud- met the inclusion criteria.
series—were retrieved. Studies assess- ies of interventions to prevent adverse
ing patients undergoing LP during spi- events were the description of random- Description of Studies
nal anesthesia or myelography were ex- ization and the ability to extract rel- Fifteen randomized trials were identi-
cluded because these procedures are evant patient data. For studies of test fied with sample sizes ranging from 44
clinically different from a diagnostic LP. accuracy, data were extracted on the ref- to 600 people. Eight studies had sample
Smaller amounts of fluid are removed erence standard, the presence of blind- sizes of 100 patients or fewer.
during spinal anesthesia and myelogra- ing, the index test, and the population
phy than with diagnostic LP and fluids characteristics. Minimum inclusion cri- Performing the Procedure
are inserted during these other proce- teria for studies of test accuracy in pa- Experience of Operator. We were un-
dures. Moreover, the risk of headache tients with suspected meningitis were able to identify any randomized stud-
is greater with diagnostic LP than with the completion of an appropriate ref- ies that evaluated the impact of the ex-
spinal anesthesia.7 Interventions of in- erence standard in all patients and the perience of the clinician performing LPs
terest included those that could be used ability to extract relevant data. Differ- on clinical outcomes. Some studies we
at the time of LP, such as immediate mo- ences in assessment by the reviewers identified included experienced neu-
bilization, atraumatic needles, and re- were resolved through discussion, and rologists,23 whereas others involved stu-
insertion of the stylet. We also at- a third investigator (K.E.T.) was avail- dents under the supervision of physi-
tempted to identify studies that assessed able if necessary. cians.25 In a case series of LPs performed
the impact of positioning of the patient For the intervention studies, statis- at an urban university-affiliated hospi-
and experience of the operator. The out- tical heterogeneity was assessed using tal, the incidence of traumatic LP was
come of interest included headache oc- the method described by Woolf.17 A 15% using a definition of more than 400
curring up to 7 days after LP. random-effects model (DerSimonian red blood cells per high-powered field
To examine the accuracy of CSF and Laird) was used for quantitative and 10% using a definition of more than
analysis in patients with suspected acute data. For the studies of test accuracy, 1000 red blood cells.26 However, the
bacterial meningitis, we included stud- LRs were calculated using the random- level of training and specialty of all phy-
ies of predominantly adult popula- effects model. Statistical analyses were sicians were not recorded. One retro-
tions and those that described use of an conducted using R: A Language and En- spective study compared the inci-
appropriate reference standard (eg, CSF vironment for Statistical Computing and dence of traumatic LP at the end of the
culture or bacterial antigen) in all pa- the rmeta contributed package. R is an resident academic year when house-
tients. In addition, primary data or ap- open-source dialect of the S language staff are more experienced with that at
propriate summary statistics had to be (S was developed by AT&T) that is the start of the next year when new
available in the studies. maintained by a core team (http://www housestaff begin training. Using a cut-
2014 JAMA, October 25, 2006—Vol 296, No. 16 (Reprinted) ©2006 American Medical Association. All rights reserved.

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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE

off of 1000 red blood cells/µL, there was matic needles (ARR, 23%; 95% CI, 6%- atraumatic needle was used (ARI, 4.9%;
no difference in risk of traumatic LP be- 40%). There are no data available on 95% CI, −13% to 3.4%).31-33 One study
tween experienced housestaff (14%) how often an introducer was used with found an increased risk of requiring 4
and inexperienced housestaff (12%).27 atraumatic needles or its impact. attempts with an atraumatic needle
In a prospective cohort of 501 patients Three of these studies, which in- compared with standard needle (ARI,
who underwent LP either by a nurse, volved 296 patients, included data on 14%; 95% CI, 3.1%-25%).32 This study
physician, resident, or medical stu- the number of attempts required to also included data on backache and
dent, there was no significant differ- complete the LP when using an atrau- found no increased risk with the atrau-
ence in the risk of post-LP headache matic needle.31-33 There was no signifi- matic needle (ARR, 7.4%; 95% CI, −12%
among the 3 groups.28 We found no data cant heterogeneity among these stud- to 27%) despite requiring more at-
on the number of LPs required to dem- ies (␹ 22 = 0.46, P = .80). There was a tempts with an atraumatic needle.
onstrate or maintain proficiency. nonsignificant increase in the risk of re- These data on backache and number of
Positioning of Patient. We were un- quiring 2 or more attempts when an attempts required with an atraumatic
able to identify any studies that evalu-
ated the success of LP with different pa- Figure 1. Types of Lumbar Puncture Needles
tient positions or the impact of patient
positioning on the risk of adverse
events. One study assessed the inter-
spinous distance to determine the im- Needle
Stylet
pact of positioning. Measurement of the
interspinous distance was conducted in
16 patients who were placed in 3 po-
sitions (lateral recumbent with knees
to chest; sitting and bent forward over Standard Needle
an adjustable bedside stand; and sit-
ting with feet supported and chest rest- Atraumatic Needle
ing on the knees).29 The interspinous
distance was greatest when the patient
was placed in the sitting position with
feet supported.
Needle Choice and Number of
Attempts. Five studies with data from
587 patients compared atraumatic
Sprotte or Pajunk needles with stan-
Two types of lumbar puncture needles are available—the atraumatic (Sprotte or Pajunk) needle and the stan-
dard Quincke needles (FIGURE 1) dur- dard (Quincke) needle. Either the 22-gauge or 20-gauge atraumatic needle, with or without an introducer,
ing diagnostic LP.30-34 One of these stud- can be used for diagnostic lumbar puncture. Use of an atraumatic needle compared with a standard needle
ies 32 described the randomization and use of a 26-gauge standard needle compared with a 22-gauge standard needle have been shown to be
associated with reduced risk of headache after lumbar puncture.37,38
method and 4 studies30-33 described the
use of blinded outcomes assessment.
Three studies provided data for inten- Figure 2. Atraumatic vs Standard Needles and Occurrence of Any Headache
tion-to-treat analysis.30-32
No. of Patients
There was a nonsignificant decrease With Headache/
in the risk of headache among patients Total No. of Patients
Atraumatic Standard
who underwent diagnostic LP with an Atraumatic Standard Odds Ratio Needle Needle
atraumatic needle (absolute risk reduc- Source Needle Needle (95% Confidence Interval) Better Better
Kleyweg et al,33 1998 3/49 16/50 0.14 (0.04-0.51)
tion [ARR], 12.3%; 95% CI, −1.72% to Lenaerts et al,30 1993 7/26 2/35 6.08 (1.14-32.28)
26.2%]). There was statistically signifi- Muller et al,31 1994 5/50 15/50 0.26 (0.09-0.78)
cant heterogeneity among these trials Strupp et al,34 2001 14/115 28/115 0.43 (0.21-0.87)
Thomas et al,32 2000
(␹42=13.3, P⬍.01). The heterogeneity ap- 21/49 31/48 0.41 (0.18-0.93)

peared to be due primarily to the small Overall 50/289 92/298 0.46 (0.19-1.07)
study (n = 61) by Lenaerts and col-
leagues (FIGURE 2) with only 9 out-
0.10 1.00 10.00
come events.30 One study32 included Odds Ratio
data on severe headache and found this
risk significantly decreased with atrau- The size of the data markers reflects the size of the study.

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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE

bed rest, the results of these studies


Figure 3. Mobilization vs Bed Rest and Occurrence of Any Headache
were excluded from further analysis.42-45
No. of Patients
With Headache/ Supplementary Fluids
Total No. of Patients
Odds Ratio Mobilization Bed Rest
In a study of 100 patients undergoing
Source Mobilization Bed Rest (95% Confidence Interval) Better Better diagnostic LP, Dieterich assessed the ef-
Dieterich and Brandt,40 1985 34/82 34/78 0.92 (0.49-1.72)
fects of drinking 1.5 L vs 3 L of fluids
Johansson et al,41 1992 4/26 2/23 1.91 (0.32-11.54)
Vilming et al,25 1998 70/150 79/150 0.79 (0.5-1.24) per day on risk of post-LP headache.45
Vimala et al,39 1998 15/104 19/104 0.75 (0.36-1.58) No details were provided on the method
of randomization or the use of blinded
Overall 123/362 134/355 0.84 (0.6-1.16) outcomes assessors. The number of out-
comes events was too small to detect a
0.10 1.00 10.00 difference between these groups (risk
Odds Ratio difference, 0.0; 95% CI, ARI 18.8%-
ARR 18.8%). Sudlow and Warlow46
The size of the data markers reflects sample size of the study.
conducted a systematic review of mo-
bilization and fluids for preventing
tion.38 No details were provided on the post-LP headache and found no effect
Table 1. Reference Values for Adult
Cerebrospinal Fluid52 method of randomization or the use of on post-LP headache.
Cerebrospinal
blinded outcomes assessment. Fewer pa-
Fluid Variable Value tients who underwent LP with reinser- Interpreting the Results
Pressure 60 to 180 mm H2O; tion of the stylet experienced headache Maneuvers During the Procedure. Nor-
6 to 14 mm Hg (ARR, 11%; 95% CI, 6.5%-16%). It is
Glucose 45-80 mg/dL (2.5-4.4 mal resting CSF pressure is assumed to
mmol/L) postulated that a strand of arachnoid be 60 to 180 mm of H2O or 6 to 14
Protein 15-45 mg/dL could enter the needle along with the out
Blood-glucose ratio ⱖ0.6 mm Hg.47,48 In the single identified
White blood cell count ⬍5/µL flowing CSF and if the stylet is not re- study, CSF pressure changed little (⬍1.1
Gram stain No organisms placed, the strand may be threaded back mm of water) with flexion of the lower
Cytology No atypical cells
through the dura during removal of the extremities.49 Various maneuvers, such
needle, producing prolonged leakage of as compressing the abdomen or the
needle were secondary outcomes of this the CSF. By replacing the stylet before jugular vein (Queckenstedt’s maneu-
study and should be further evaluated removing the needle, the strand would ver50), can increase CSF pressure.51 An
in larger trials. be pushed out and cut, reducing the risk obstruction to CSF flow prevents the
Recently published guidelines from of continued leakage and the resulting normal rise and fall in pressure (posi-
the American Academy of Neurology headache.38 tive Queckenstedt), but we were un-
support the use of atraumatic needles able to find any studies describing the
when completing diagnostic LPs to re- Bed Rest After the Procedure accuracy of this maneuver for detec-
duce the risk of post-LP headache.35 In Four studies with data from 717 pa- tion of CSF outflow obstruction.
an earlier version of this guideline, they tients compared immediate mobiliza-
reported that LP trays containing the tion with bed rest lasting 4 hours for Laboratory Tests
Sprotte needle are the same price as reducing post-LP headache.25,39-41 One Although CSF samples can be sub-
those containing the Quincke.36 study provided some details on the jected to various analyses, we focused
One study of 100 patients com- method of randomization.25 This study on test results immediately relevant and
pared use of a 26-gauge Quincke needle also described use of blinded out- useful to generalist physicians when
vs a 22-gauge Quincke needle.37 Blinded comes assessors. Two of the 3 studies evaluating a patient suspected of hav-
outcomes observers were used and data provided data for an intention-to- ing bacterial meningitis. Normal CSF
were provided for intention-to-treat treat analysis.25,40 values are listed in TABLE 1, but these
analysis. The risk of headache was sig- There was no significant heterogene- values may vary across different labo-
nificantly reduced with a smaller needle ity among these studies (␹ 23 = 1.04, ratories.52 We found 460 diagnostic ar-
(ARR, 26%; 95% CI, 11%-40%). P=.79). There was a nonsignificant de- ticles in our literature search, and 6 met
crease in the risk of headache in pa- inclusion criteria (TABLE 2). One ex-
Reinsertion of Stylet tients who were mobilized after LP (ARR, pert suggests that the white blood cell
Strupp and colleagues studied 600 pa- 2.9%; 95% CI, ARI 3.4%-ARR 9.3%]; count be corrected for the presence of
tients and compared the effects of rein- FIGURE 3) Three studies looked at head red blood cells by subtracting 1 white
sertion of the stylet before removing the positioning during bed rest, but given blood cell from the total white blood
atraumatic needle with no reinser- that there was no significant effect from cell count in the CSF for every 700 red
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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE

blood cells.2 He also states that a single vided into a derivation and validation McKinney and colleagues63 obtained
polymorphonuclear cell in the CSF with set, but data from a large number of similar results in their retrospective
a white blood cell count of less than 5 charts (94/214) in the derivation set had review.
µL is considered normal. Steele and col- missing data and were excluded from In the only prospective validation
leagues suggest rapid analysis of CSF the analysis. And, the technique used that we were able to identify, Baty and
and noted that neutrophil counts can for CSF cell count changed during the colleagues64 assessed Hoen’s rule in a
decrease by 50% within 2 hours of study period, which could influence the sample of 109 patients aged 1 to 85
collection.59 results of this study. The accuracy as years with acute community-acquired
We found 3 studies that met the in- measured by the area under the re- meningitis. Data are only available in
clusion criteria and that described the ceiver operating curve (AUC) was 0.97 patients with bacterial and viral men-
accuracy of CSF Gram stain for diag- for the validation set. ingitis, and thus the specificity of the
nosing bacterial meningitis.53-55 None Hoen and colleagues61 attempted to model cannot be calculated. The sen-
of these studies appeared to be pro- validate the above rule in a retrospec- sitivity of their computed model was
spective. All studies reported sensitiv- tive review and used the same data to 80% for the diagnosis of bacterial men-
ity of Gram stain and 1 study reported generate their own decision rule ingitis. For this decision rule to be rec-
specificity of this test53 (TABLE 3). If bac- (Table 5) that included 4 different clini- ommended in clinical practice, it needs
teria are seen on Gram stain, it helps cal variables. In their validation of the to be validated prospectively in larger
diagnose bacterial meningitis but if this work by Spanos and colleagues, the AUC populations with broader disease
test is negative, bacterial meningitis can- was 0.98 while that for their derived spectrum.65
not be ruled out. equation was 0.99. In another retrospec- Brivet and colleagues66 completed a
We identified 4 studies that met the tive review of patients with meningitis, retrospective study and found that the
inclusion criteria and that reported on Leblebicioglu and colleagues62 assessed presence of at least 1 sign of severity of
the accuracy of biochemical analysis of the rules by Hoen and Spanos and the disease at the time referral and a CSF
CSF in patients with suspected central AUC was 0.99 and 0.95, respectively. neutrophil count of more than 1000/µL
nervous system infection55-58(Table 2
and TABLE 4). Only 1 study of CSF
Table 2. Studies Assessing Cerebrospinal Fluid Analysis in Patients With Suspected Central
white blood cell counts met our strict Nervous System Infection
inclusion criteria. A CSF white blood
Source Study Design Sample Size Age Reference Standard
cell count of 500/µL or higher in- Dunbar et al,53 Retrospective 2635 CSF Adults Positive CSF culture
creases the likelihood of meningitis (LR, 1998 samples
15; 95% CI, 10-22), whereas a count Wasilauskas and Retrospective 80 CSF Adults Positive CSF culture
less than 500/µL lowers the likelihood Hampton,54 samples or bacterial antigen
1982
(LR, 0.3; 95% CI, 0.2-0.4).56
Lannigan et al,55 Cohort 434 16-86 y Positive CSF culture
A CSF–blood glucose ratio of 0.4 or 1980 (not clear if
less was accurate for diagnosing bac- prospective)
terial meningitis (LR, 18; 95% CI, 12- Lindquist et al,56 Prospective 710 ⬎2 mo but Positive CSF culture
1988 cohort majority adults or bacterial antigen
27), whereas a normal CSF–blood glu-
Briem,57 1983 Cohort 266 90% 15 y or older Positive CSF culture
cose ratio made this diagnosis less likely (not clear if or bacterial antigen
(LR, 0.31; 95% CI, 0.21-0.45).56,57 A prospective)
CSF lactate level of 31.53 mg/dL or Komorowski Retrospective 562 Adults Positive CSF culture
et al,58 1986
more (ⱖ3.5 mmol/L) was accurate for
Abbreviation: CSF, cerebrospinal fluid.
diagnosing bacterial meningitis (LR, 21;
95% CI, 14-3255-57; Table 4), whereas
a CSF lactate level of less than 31.53 Table 3. Accuracy of Cerebrospinal Gram Stain in Patients With Suspected Bacterial
mg/dL (⬍3.5 mmol/L) makes the di- Meningitis*
agnosis of bacterial meningitis less likely Likelihood Likelihood
Ratio for Ratio for
(LR, 0.12; 95% CI, 0.07-0.23). Sensitivity, % Specificity, % Positive Test Negative Test
Study (95% CI) (95% CI) (95% CI) (95% CI)
Prediction Models Dunbar et al,53 1998 86 (74-92.6) 100 (lower 95 737 (230-2295) 0.14 (0.08-0.27)
confidence
Spanos and colleagues60 developed a limit 99.7)
prediction rule for diagnosing bacte- Wasilauskas and 60 (47-71) ... ... ...
rial meningitis. This rule (TABLE 5) was Hampton,54 1982
derived from a retrospective chart re- Lannigan et al,55 1980 56 (34-75) ... ... ...
view of patients with a final diagnosis Abbreviation: CI, confidence interval.
*Ellipses indicate that data are not available.
of acute meningitis. The sample was di-
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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE

not be attempted at higher levels in or-


Table 4. Accuracy of Cerebrospinal Fluid Biochemical Analysis in Patients With Suspected
Bacterial Meningitis der to avoid the conus medullaris. There
Positive Negative is no evidence to guide the clinician
Likelihood Likelihood about whether the L3-L4 or L4-L5 in-
CSF Test Ratio (95% CI) Ratio (95% CI) terspace is the optimal site for the ini-
White blood cell count ⱖ500/µL56 15 (10-22) 0.30 (0.20-0.40) tial attempt, which is a topic high-
Glucose ⬎39.6 mg/dL (⬎2.2 mmol/L)56 23 (13-40) 0.50 (0.40-0.60)
lighted for future research. The
Blood glucose ratio ⱕ0.456 18 (12-27) 0.31 (0.21-0.45)
performance of LP may occur at L5-S1
Blood glucose ratio ⬍0.4
Briem,57 1983* 145 (20.4-1029) 0.25 (0.15-0.40) because there are fewer nerve roots and
Lactate ⬎27 mg/dL (⬎3 mmol/L) a relatively larger interspace. The
Komorowski et al,58 1986 2.9 (2.4-3.5) 0.20 (0.06-0.50) spinous process superior to the cho-
Lactate ⱖ31.5 mg/dL (ⱖ3.5 mmol/L) sen interspace should be palpated. The
Lannigan et al,55 1980 13 (8.6-20) 0.20 (0.06-0.50)
needle should be inserted about 1 cm
Lindquist et al,56 1988 25 (16-38) 0.12 (0.06-0.20)
inferior to the tip of this process.68
Briem,57 1983† 38 (15-94) 0.01 (0.001-0.20)
Wearing sterile gloves and a mask,
Summary 21 (14-32) 0.12 (0.07-0.23)
the clinician should cleanse the punc-
Abbreviations: CI, confidence interval; CSF, cerebrospinal fluid.
*n = 245. ture site with an antiseptic solution by
†n = 218. applying it in a circular motion that
starts at the center of where the punc-
were predictors of bacterial meningi- average, 6 out of 10 people may de- ture will occur. Sterile drapes can be
tis. Severity was defined by the pres- velop a transient headache after LP and applied, leaving the puncture site
ence of at least 1 of the following: al- that up to 4 out of 10 people can ex- exposed. Palpate the identified
tered consciousness, seizure, focal perience temporary backache. Pa- spinous process again and with 2 to 3
neurological findings, and shock. Be- tients should be asked if they are aller- mL of local anesthetic (eg, lidocaine),
cause this study was retrospective, rel- gic to any medications including local infiltrate the patient’s skin and deeper
evant laboratory data was not avail- anesthetic. For the anxious patient, tissues allowing 1 to 2 minutes for this
able for all patients. And, this model has some experts suggest that a small dose to take effect. An atraumatic needle
not been prospectively validated in an of anxiolytic (eg, lorazepam) may be does not have the same cutting edge as
independent population. given prior to the procedure if the pa- a standard needle so it may be prefer-
tient wishes. able to use an introducer to puncture
How Should the Procedure In the absence of any focal neuro- the skin prior to insertion of the
Be Performed? logical findings, altered mentation or needle if this needle type is used.
Ideally, a successful LP should meet the papilledema, the LP can be performed Introduce the spinal needle (using the
following criteria: (1) obtain suffi- without first completing a CT scan.12,13 same track that was used for the anes-
cient CSF on the first attempt, (2) oc- If a CT scan is requested before the LP thetic) and advance it horizontally
curs without trauma (ie, CSF contain- when bacterial meningitis is sus- while aiming toward the umbilicus to
ing ⬍1000 red blood cells per high pected, antibiotic therapy should be a depth of about 2 cm. If bone is
powered field), (3) occurs with mini- started immediately and should not encountered, withdraw the needle to
mal discomfort to the patient during await completion of the CT scan. If pos- the subcutaneous position and reinsert
and after the procedure, and, (4) oc- sible, blood cultures should be taken at a slightly different angle. Continue
curs without serious adverse events prior to starting antibiotics. to advance the needle until a pop is
such as cerebral herniation. The fol- The LP is usually completed with the felt, indicating penetration of the liga-
lowing description of the method to patient in the lateral recumbent posi- mentum flavum. The needle should
perform an LP considers the best avail- tion with his/her back at the edge of the now be in the subarachnoid space.
able evidence and expert opinion to fa- bed to minimize curving of the spine When the stylet is withdrawn, clear
cilitate successful LP completion. (FIGURE 4). Both legs should be flexed fluid should drip. If no fluid emerges,
The procedure and its risks should toward the chest and the neck should rotate the needle to ensure that no flap
be explained to the patient and in- also be slightly flexed. The patient’s of dura is blocking flow of CSF. If
formed consent obtained if relevant in shoulders and pelvis should be verti- there is still no fluid, reinsert the stylet
the practice setting. The description cal to the bed. In this position, an imagi- and advance the needle slightly, with-
should include how the procedure will nary line connecting the patient’s pos- drawing the stylet after each move-
be performed, why it is being per- terior superior iliac crests would cross ment. Pain radiating down either leg
formed, what complications may oc- the L4-L5 interspace (Figure 4). Lum- indicates that the needle is too lateral
cur, and how these can be treated. For bar puncture can occur in the L3-L4, and has touched nerve roots. If this
example, patients can be told that on L4-L5, or L5-S1 interspace.67 It should occurs, immediately withdraw the
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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE

Table 5. Studies That Developed and/or Validated Prediction Rules for Diagnosing Bacterial Meningitis*
No. of
Study Study Design Patients Age Model Accuracy
Spanos et al,60 1989 Retrospective chart Derivation ⬎1 mo PABM =
1
† AUC 0.97
review set, 120 (1 + e −L)
Hoen et al,61 1995 Retrospective chart 500 ⬎1 mo PABM =
1
‡ AUC 0.99
review (1 + e −L)
Leblebicioglu et al,62 Retrospective chart 40 NA Assessed models by Hoen and Spanos AUC 0.95 by Spanos§
1996 review AUC 0.99 by Hoen
McKinney et al,63 1994 Retrospective chart 170 ⬎17 y Assessed model by Spanos AUC 0.98
review
Baty et al,64 2000 Prospective㛳 109 1-85 y Assessed model by Hoen Sensitivity 80%
Abbreviations: AUC, area under the curve; CSF, cerebrospinal fluid; NA, not available; PABM, probability of acute bacterial meningitis; PMN, polymorphonuclear leukocytes.
*Reference standard: bacterial meningitis is present when CSF, urine, or blood tests positive or when bacterial antigen is detected in blood, urine, or CSF.
†Where L = 0.52 ⫻ number of months from August 1 −12.76 ⫻ CSF: blood glucose ratio (if ratio ⬎0.6, use 0.6) ⫹ 0.341 ⫻ (PMNs in CSF ⫻ 106/1)0.333 ⫹ 2.29 ⫻ age ⫹ 2.79
(if age ⱕ1 y), −2.71 ⫻ age ⫹ 7.79 (if 1 y ⬍age ⱕ2 y), −0.159 ⫻ age ⫹ 2.69 (if 2 y ⬍age ⱕ22 y), or ⫹ 0.1 ⫻ age = 3.01 (if age ⬎22 y).
‡Where L = 32.13 ⫻ 10−4 ⫻ CSF PMN count (106/L) ⫹ 2.365 ⫻ CSF protein (g/L) ⫹ 0.6143 ⫻ blood glucose (mmol/L) ⫹ 0.2086 ⫻ leukocyte count (109/L) −11.
§Note the units used in the equation: glucose 1 mg/dL. To convert to mmol/L, multiply by 0.0555.
㛳Excluded those with encephalitis and in those for whom the diagnosis was obvious (eg, cloudy CSF or positive Gram stain).

needle almost to the skin, recheck the has been completed, the stylet should post-LP headache of less than 60% and
patient’s position, and reinsert the be reinserted prior to removal of the of backache of less than 40%. How-
needle in the mid line. If this process needle. A bandage may be applied to the ever, these figures represent the aver-
fails, move down 1 interspace and try puncture site and the patient allowed age risk of these events and thus can-
again. If this fails, the procedure to ambulate. not be considered as benchmarks.73
should be attempted by another per- To date, there is little evidence to
son; alternatively it can be done under How Should This Procedure guide the teaching of this procedure.
fluoroscopic guidance. If the LP Be Taught or Learned? Simulators have been developed, but
attempt is unsuccessful with the Recent surveys of clinical practice sug- they have not been rigorously evalu-
patient in the lateral position, it may gest variation in LP technique. A 1996 ated.74 In one randomized trial of a
be attempted with the patient sitting survey of senior registrars in all depart- Web-based educational tool, 14 nov-
upright.50 However, this position does ments of neurology and neurosurgery ice trainees were randomized to re-
not permit accurate measurement of in the United Kingdom found that 15% ceive Web-based training or no train-
the CSF pressure.50,69 of respondents reported using atrau- ing.75 The Web-based training module
When flow of CSF is seen, pressure can matic needles and that 73% recom- provided virtual simulation of an LP.
be measured by connecting a manom- mended bed rest for up to 6 hours af- Both groups completed pre- and post-
eter directly to the needle or via a 2- or ter completion of the LP.70 A similar LPs on a synthetic mannequin. Inves-
3-way stopcock. The 0 mark on the survey of 2287 practicing neurolo- tigators found an improvement in per-
manometer should be held at the level gists in the United States found that 2% formance of LP with completion of the
of the spinal needle and the tube held ver- used atraumatic needles.70 Neurolo- training module. There was no assess-
tically. Normally, there will be variation gists did not use atraumatic needles due ment of the procedural skills on pa-
in the pressure with respiration. to lack of knowledge of them or be- tients or of the risk of post-LP compli-
The manometer contents can be re- cause the needles were not available for cations. This evidence highlights the
leased for collection and analysis. Ad- use in their institution.71 need to evaluate teaching the perfor-
ditional CSF can be collected for the re- The American Board of Internal mance of LP to ensure clinical compe-
quired investigations. Typically, the Medicine recommends 3 to 5 LPs as a tence is achieved and maintained.
examiner prepares 3 to 4 collection minimum standard for ensuring com-
tubes. The initial CSF sample is placed petence in completing LPs.72 How- SCENARIO RESOLUTION
into a tube labeled for biochemistry, and ever, trainees report that they needed Our patient had a fever, confusion, and
tube number 2 is for bacterial studies to complete 6 to 10 procedures to feel neck stiffness. Many clinicians might
(Gram stain, culture, and sensitivity). comfortable with their performance.72 proceed immediately to LP to rule out
Cell counts can be done on tube num- Based on the evidence reviewed in meningitis. However, we weren’t able
ber 3, and the fourth tube can be used this article, some targets could be sug- to complete a full neurological exami-
for cytology or for other tests that might gested to help clinicians assess the qual- nation because our patient was unable
be done when considering other diag- ity of their LP performance. A success- to cooperate with the assessment. As
noses. These tests will vary depending ful LP would be indicated by obtaining discussed in this article, evidence sug-
on the differential diagnosis for the in- sufficient CSF fluid for analysis on the gests that her altered mental state and
dividual patient. Once CSF collection first attempt and by achieving risks of age and our inability to confirm the ab-
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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE

sence of a focal neurological finding are conundrum even though the inci- meningitis, we obtained blood work in-
appropriate indications for a CT scan dence of intracranial lesions with such cluding complete blood count, glu-
to rule out an intracranial lesion. This presentations is low. Because our clini- cose, and cultures and initiated imme-
situation describes a common clinical cal findings were strongly suggestive of diate antibiotic therapy. We decided to

Figure 4. Anatomical Considerations During Lumbar Puncture

A Patient Position and Identification of Bony Landmarks

Vertical Alignment of
Shoulders and Pelvis
Possible Needle Insertion Sites

L3 L4 L5 S1

L4

Line Between Superior Border


of the Posterior Iliac Crests
Intersecting L4 Spinous Process

B Hand Position, Needle Direction, and Anatomical Relationships

L1
Nerve Root
A
N
TE
RI Ligamentum
L2 OR R Flavum
Vertebral Body IO
R
Cauda Equina P
E
Spinal L3 S
U
Cord
L4
Subarachnoid
L5 Space
Conus
Medullaris Interspinous
TOP VIEW Cauda Arachnoid Ligament
Equina
2 cm

Dura Mater Supraspinous


Cerebrospinal Ligament
Fluid (Overlying
1c Spinous Process)
m
Spinous Epidural
Process Space

Lumbar Puncture
Needle

Lumbar puncture is usually performed with the patient in the lateral recumbent position. To avoid rotation of the vertebral column, align the patient’s shoulders and
pelvis in a plane perpendicular to the bed. A line connecting the superior border of the posterior iliac crests intersects the L4 spinous process or the L4-L5 interspace.
Insert the lumbar puncture needle in the midline of the L3-L4, L4-L5 (most commonly), or L5-S1 vertebral interspace. These interspaces are below the end of the spinal
cord, which terminates at the level of L1. Angle the needle towards the patient’s umbilicus and advance it slowly. The needle will penetrate the ligamentum flavum,
dura, and arachnoid to enter the subarachnoid space, where cerebrospinal fluid is located.

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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE

obtain a CT scan (on which no mass le- Author Contributions: Dr Straus had full access to all Computed tomography of the head before lumbar
of the data in the study and takes responsibility for puncture in adults with suspected meningitis. N Engl
sion was noted) before performing an the integrity of the data and the accuracy of the data J Med. 2001;345:1727-1733.
LP. Given her confusion and uncer- analysis. 14. Ruff RL, Dougherty JH. Complications of lumbar
Study concept and design: Straus. puncture followed by anticoagulation. Stroke. 1981;
tain neurological status, we suggested Acquisition of data: Straus, Holroyd-Leduc. 12:879-881.
ambulation with assistance. We used an Analysis and interpretation of data: Straus, Thorpe, 15. Waldman W, Laureno R. Precautions for lumbar
atraumatic needle and completed the Holroyd-Leduc. puncture: a survey of neurologic educators. Neurology.
Drafting of the manuscript: Straus. 1999;52:1296-1299.
procedure with the patient in the left Critical revision of the manuscript for important in- 16. Vavricka SR, Walter RB, Irani S, et al. Safety of
lateral recumbent position. Cerebrospi- tellectual content: Straus, Thorpe, Holroyd-Leduc. lumbar puncture for adults with acute leukemia and
Statistical analysis: Straus, Thorpe. restrictive prophylactic platelet transfusion. Ann
nal fluid was sent for cell count, Gram Administrative, technical, or material support: Straus. Hematol. 2003;82:570-573.
stain, culture, protein, glucose, and lac- Financial Disclosures: None reported. 17. Woolf B. On estimating the relation between blood
Funding/Support: Dr Straus is supported by a Tier 2 group and disease. Ann Hum Genet. 1955;19:251-253.
tate. Results showed a white blood cell Canada Research Chair; Mr Thorpe and Dr Holroyd- 18. Carbaat PA, Van Crevel H. Lumbar puncture head-
count of 5000/µL and a CSF–blood- Leduc are supported by the Knowledge Translation ache: controlled study on the preventive effect of 24
Program at the University of Toronto. hours’ bed rest. Lancet. 1981;2:1133-1135.
glucose ratio of 0.2, helping us to di- Role of the Sponsor: There was no external funding 19. Aamodt A, Vedeler C. Complications after LP re-
agnose bacterial meningitis. obtained for the design and conduct of the study, the lated to needle type: pencil-point versus Quincke. Acta
collection, management, analysis, or for the interpre- Neurol Scand. 2001;103:396-398.
BOTTOM LINE tation of the data; or for the preparation, review, or 20. Braune HJ, Huffmann G. A prospective double-
approval of the manuscript. blind clinical trial comparing the sharp Quincke needle
Lumbar punctures to assess meningi- Acknowledgment: We thank Darlyne Rath, Laure (22G) with an “atraumatic” needle (22G) in the in-
Perrier, and Desiree Chanderbhan for their assis- duction of post-lumbar puncture headache. Acta Neu-
tis in adults should be performed un- tance in the search and retrieval of relevant articles rol Scand. 1992;86:50-54.
der sterile conditions with the patient and the preparation of the manuscript as part of their 21. Kovanen J, Sulkava R. Duration of postural head-
normal duties. Richard Bedlack, MD, PhD, Division of
placed in the lateral recumbent posi- Neurology, and Sheri Keitz, MD, PhD, Division of Gen-
ache after lumbar puncture: effect of needle size.
Headache. 1986;26:224-226.
tion and their knees flexed. Alterna- eral Internal Medicine, Duke University, Durham, NC, 22. Spriggs DA, Burn DJ, Cartlidge NE, Bates D. Is bed
tively, the patient could sit up and lean and Kaveh Shojania, MD, Department of Medicine, rest useful after diagnostic lumbar puncture? Post-
University of Ottawa, Ottawa, Ontario, who pro- grad Med J. 1992;68:581-583.
forward with his/her feet supported to vided useful feedback and suggestions on earlier drafts 23. Strupp M, Brandt T. Should one reinsert the
increase the interspinous space. For of the manuscript. We also thank Janis Miyasaki, MD, stylet during lumbar puncture? N Engl J Med. 1997;
FRCPC, Department of Neurology, for comments on 336:1190.
most patients, a CT scan of the head to the figure. They received no compensation for their 24. Engelhardt A, Oheim S, Neundorfer B. Post-
rule out mass lesion is not required be- reviews of the manuscript.
lumbar puncture headache: experiences with Sprotte’s
fore the LP and the clinical examina- atraumatic needle. Cephalalgia. 1992;12:259.
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